Co-reporter:Ri Zhou, Zai-Qun Liu
Archives of Biochemistry and Biophysics 2017 Volume 631(Volume 631) pp:
Publication Date(Web):1 October 2017
DOI:10.1016/j.abb.2017.08.002
•Antioxidants are synthesized as dimer, trimer, and tetramer.•Antioxidant effects were enhanced by tetrameric structural style.•Synergistic enhancement effect was provided to explain the antioxidant effect.To overcome the problem on the relationship of antioxidative effect with the branch number in a tetramer, we herein designed a series of antioxidants with pentaerythritol, glycerol, and ethylene glycol as the cores, and gallic, ferulic, caffeic, and p-hydroxybenzoic acids as the antioxidative moieties. In the case of DNA oxidation mediated by 2,2′-azobis(2-amidinopropane hydrochloride, AAPH), it was found that the stoichiometric factor (n) of a carboxylic acid increased rapidly when the acid was esterified with ethylene glycol, glycerol, and pentaerythritol to form a dimer, trimer, and tetramer, respectively. Interestingly, the coefficient in the equation of n∼{branch} ({branch} referred to the number of branches) was higher than one, indicating that the antioxidative effect was enhanced more promptly than the increase of the number of branches. Meanwhile, tetramer exhibited high intercalation effect with DNA strand. Therefore, additionally antioxidative effect was ascribed to the tethering effect resulting from tetrameric structure and strong intercalation with DNA strand generated by tetramer.Download high-res image (165KB)Download full-size image
Co-reporter:Peng-Fei Zhao, Zai-Qun Liu
European Journal of Medicinal Chemistry 2017 Volume 135(Volume 135) pp:
Publication Date(Web):28 July 2017
DOI:10.1016/j.ejmech.2017.04.041
•2-Isocyano glucose was applied to carry out Ugi four-component-reaction (Ugi 4CR).•Gallic, ferulic, caffeic, or p-hydroxylbenzoic acids, aniline (or benzylamine and p-aminophenol), and formaldehyde acted as other reagents.•The produced bisamindes were allowed protecting DNA against peroxyl and hydroxyl radical as well as Cu2+/glutathione-mediated DNA oxidations.•Ugi adducts containing glucose moiety exhibited higher antioxidative activities than those glucose-free analogs.The Ugi four-component-reaction (Ugi 4CR) allowed synthesizing bisamide from carboxylic acid, aldehyde, amine, and isocyanide in one-pot operation. However, introducing 2-isocyano glucose into the Ugi 4CR and investigating the inhibitory effects of Ugi adducts against radical-induced oxidation of DNA remained technical challenges. We herein applied 2-isocyano glucose (acetylation of hydroxy groups) to perform a catalyst-free Ugi 4CR at room temperature. The gallic, ferulic, caffeic, or p-hydroxybenzoic acids, aniline (or benzylamine and p-aminophenol), and formaldehyde acted as reagents. In the case of inhibiting DNA oxidations induced by 2,2’-azobis(2-amidinopropane hydrochloride) (AAPH), hydroxy radical, and Cu2+/glutathione, the Ugi adduct containing glucose moiety exhibited higher antioxidative activities than the structural analog without glucose moiety involved. It was also proved that high antioxidative property was owing to hydroxy groups in glucose moiety. Therefore, sugar-appended Ugi adducts might hold promising inhibitors for DNA oxidation.Download high-res image (190KB)Download full-size image
Co-reporter:Jia-Feng Chen, Zai-Qun Liu
Tetrahedron 2016 Volume 72(Issue 15) pp:1850-1859
Publication Date(Web):14 April 2016
DOI:10.1016/j.tet.2016.02.042
The o-phenylenediamine, aldehyde, and 2,4,4-trimethylpentan-2-yl isocyanide performed a Groebke 3CR to afford 2-aminoquinoxaline, which can react with an aldehyde and t-butyl isocyanide via another Groebke 3CR to give imidazo[1,2-a]quinoxaline. Exchanging two aldehydes in the sequential Groebke 3CR led to a couple of imidazo[1,2-a]quinoxaline isomer, in which the aldehyde moiety located at 2- or 4-position. The ferrocenyl group at 4-position in imidazo[1,2-a]quinoxaline was found to be active in trapping galvinoxyl radical, while the phenolic hydroxyl group at 2-position played a synergistic role with 4-ferrocenyl or 4-flavonyl group in scavenging 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH). In addition, 4-ferrocenyl with N,N-dimethylaminophenyl group at 2-position was able to quench 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+). Moreover, the combination of 4-ferrocenyl with 2-phenyl group (bearing para-N,N-dimethylamino or hydroxyl group) exhibited high inhibitory effect on DNA oxidation induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH).
Co-reporter:Liang-Liang Bao ;Dr. Zai-Qun Liu
ChemMedChem 2016 Volume 11( Issue 15) pp:1617-1625
Publication Date(Web):
DOI:10.1002/cmdc.201600205
Abstract
The inhibitory effect of resveratrol on DNA oxidation caused by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) was found to be enhanced if the C=C bond in resveratrol was converted into tetrahydropyrrole by reaction with azomethine ylide (CH2=N+(CH3)CH2−). This encouraged us to explore whether the inhibitory activities of other stilbenes could also be increased by the same method. We found that the inhibitory effects of the tetrahydropyrrole derivatives on AAPH-induced oxidation of DNA were higher than those of the corresponding stilbenes, because the tetrahydropyrrole motif can provide hydrogen atoms to be abstracted by radicals. Therefore, the tetrahydropyrrolization offered an advantage for enhancing the antioxidant effects of stilbenes. Notably, (CH3)3SiCH2N(CH3)CH2OCH3 (in the presence of CF3COOH) and (CH3)3NO (in the presence of LiN(iPr)2) can be used to generate azomethine ylide for the tetrahydropyrrolization of stilbenes containing electron-withdrawing and -donating groups, respectively.
Co-reporter:Gao-Lei Xi, Zai-Qun Liu
European Journal of Medicinal Chemistry 2015 Volume 95() pp:416-423
Publication Date(Web):5 May 2015
DOI:10.1016/j.ejmech.2015.03.061
•8-Phenyl-6-ferrocenyl-4-methyl-2H-pyrano[3,2-g]quinolin-2-ones were synthesized by Povarov reaction.•Radical-scavenging effectiveness were evaluated by trapping ABTS+ and DPPH.•Inhibitory effects on AAPH-induced oxidation of DNA were investigated.•Antioxidant effect was generated by ferrocenyl group and enhanced by electron-donating groups.Fifteen 8-substituted-phenyl-6-ferrocenyl-4-methyl-2H-pyrano[3,2-g]quinolin-2-ones were synthesized via Povarov three-component reaction, in which the substituted aromatic aldehydes reacted with ferrocenylacetylene and 7-amino-4-methylcoumarin in the presence of Ce(OTf)3 as the catalyst. The obtained coumarin-fused quinolines were applied to quench 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+) and 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and to inhibit 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. It was found that the ferrocenyl group attaching to pyrano[3,2-g]quinolin-2-one scaffold can trap radicals and inhibit DNA oxidation even in the absence of phenolic hydroxyl group. The inhibitory effects on radicals and DNA oxidation can be further enhanced by the electron-donating groups such as p-(N,N-dimethyl amino)phenyl, ferrocenyl, and furan-2-yl group at 8-position. Therefore, ferrocenyl-substituted pyrano[3,2-g]quinolin-2-one skeleton together with electron-donating groups became a novel structural style for antioxidants.Antioxidant effects of 8-substituted-phenyl-6-ferrocenyl-4-methyl-2H-pyrano[3,2-g]quinolin-2-ones were generated by ferrocenyl group and enhanced by electron-donating groups.
Co-reporter:Gao-Lei Xi and Zai-Qun Liu
Journal of Agricultural and Food Chemistry 2015 Volume 63(Issue 13) pp:3516-3523
Publication Date(Web):March 31, 2015
DOI:10.1021/acs.jafc.5b00399
Two coumarin skeletons can form chromeno[3,4-c]chromene-6,7-dione by sharing with the C═C in lactone. The aim of the present work was to explore the antioxidant effectiveness of the coumarin-fused coumarin via six synthetic compounds containing hydroxyl and N,N-dimethylamino as the functional groups. The abilities to quench 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+•), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical revealed that the rate constant for scavenging radicals was related to the amount of hydroxyl group in the scaffold of coumarin-fused coumarin. But coumarin-fused coumarin was able to inhibit DNA oxidations caused by •OH, Cu2+/glutathione (GSH), and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) even in the absence of hydroxyl group. In particular, a hydroxyl and an N,N-dimethylamino group locating at different benzene rings increased the inhibitory effect of coumarin-fused coumarin on AAPH-induced oxidation of DNA about 3 times higher than a single hydroxyl group, whereas N,N-dimethylamino-substituted coumarin-fused coumarin possessed high activity toward •OH-induced oxidation of DNA without the hydroxyl group contained. Therefore, the hydroxyl group together with N,N-dimethylamino group may be a novel combination for the design of coumarin-fused heterocyclic antioxidants.
Co-reporter:Jia-Feng Chen and Zai-Qun Liu
Chemical Research in Toxicology 2015 Volume 28(Issue 3) pp:451
Publication Date(Web):December 30, 2014
DOI:10.1021/tx500405b
The aim of the present work was to compare the antioxidative effect of the ferrocenyl-appended aurone with that of ferrocenyl-appended flavone; therefore, nine aurones together with the flavone-type analogues were synthesized by using chalcone as the reactant. The radical-scavenging property was evaluated by reacting with the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+·), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. The cytotoxicity was estimated by inhibiting 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. It was found that the introduction of the ferrocenyl group remarkably increased the radical-scavenging activities of aurone and flavone. Especially, the ferrocenyl group in flavones can quench radicals even in the absence of the phenolic hydroxyl group, while ferrocenyl-appended aurones can efficiently protect DNA against AAPH-induced oxidation. Therefore, the antioxidative effect was generated by the ferrocenyl group and enhanced by the electron-donating group attaching to the para-position of the ferrocenyl group. Introducing the ferrocenyl group into natural compounds may be a useful strategy for increasing the antioxidative effectiveness.
Co-reporter:Rui Wang, Zai-Qun Liu
Tetrahedron Letters 2015 Volume 56(Issue 50) pp:7028-7033
Publication Date(Web):16 December 2015
DOI:10.1016/j.tetlet.2015.11.009
Eighteen α-acyloxycarboxamides were produced by Passerini three-component reaction (3CR) in order to reveal sterically synergistic effects among various functional groups on the inhibitory properties of α-acyloxycarboxamides toward DNA oxidation and radicals. In trapping 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical and in inhibiting 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA, α-acyloxycarboxamides with gallic group exhibited significant activities, which can be further enhanced by incorporation of a ferrocenyl group (derived from ferrocenylmethyl isocyanide) at another tip of the molecule. Therefore, a large volume and electron-abundant isocyanide moiety were able to increase the inhibitory effects of phenolic hydroxyl groups derived from carboxylic acid even in a conjugation-free system.
Co-reporter:Xiao-Rui Gong, Gao-Lei Xi, Zai-Qun Liu
Tetrahedron Letters 2015 Volume 56(Issue 45) pp:6257-6261
Publication Date(Web):4 November 2015
DOI:10.1016/j.tetlet.2015.09.105
Fourteen coumarin–oxadiazole-appended phenols were synthesized, while halogen atom, methoxyl, and hydroxyl groups acted as the functional groups for testing the ability to trap 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+) and to inhibit the oxidation of DNA caused by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) and Cu2+/glutathione (GSH). The coumarin–oxadiazole-appended phenols containing the hydroxyl group were able to inhibit AAPH-induced oxidation of DNA and to quench ABTS+, and the antioxidant effectiveness depended upon the number of hydroxyl groups. Moreover, the coumarin–oxadiazole-appended phenols used herein were able to inhibit Cu2+/GSH-induced oxidation of DNA, and the inhibitory effect generated by bromide was similar to that of the hydroxyl group. In particular, the antioxidant effectiveness of para-bromide at the benzene ring even approached to that of Trolox.
Co-reporter:Gao-Lei Xi, Zai-Qun Liu
Tetrahedron 2015 Volume 71(Issue 52) pp:9602-9610
Publication Date(Web):30 December 2015
DOI:10.1016/j.tet.2015.10.080
With 2-aminopyridine or quinoline, seven aldehydes, and five isocyanides as reactants, sixteen imidazo[1,2-a]pyridines or quinolines were synthesized by using Groebke three-component-reaction (3CR). The radical-scavenging ability was evaluated by quenching 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+·), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radicals, respectively. Compounds consisting of double ferrocenyl groups coupled with quinoline and ester moieties showed good potencies for scavenging ABTS+· and DPPH, while phenolic hydroxyl groups activated the corresponding imidazo[1,2-a]pyridines to react with galvinoxyl radical. Moreover, the oxidation of DNA was caused by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), and all of the synthetic compounds were found to inhibit the DNA oxidation. Especially, the scaffold of imidazo[1,2-a]pyridine exhibited antioxidative effect on the DNA oxidation, while the most active compound was ascribed to double ferrocenyl groups incorporating with imidazo[1,2-a]quinoline. The present results showcased that the ferrocenyl group attaching to the scaffold of imidazo[1,2-a]pyridine or quinoline was beneficial for the antioxidative effect.
Co-reporter:Gao-Lei Xi, Zai-Qun Liu
European Journal of Medicinal Chemistry 2014 Volume 86() pp:759-768
Publication Date(Web):30 October 2014
DOI:10.1016/j.ejmech.2014.09.044
•Twenty-two ferrocenyl quinolines were synthesized by solvent-free Povarov reaction.•Ferrocenyl instead of hydroxyl group can reduce radicals directly.•Ferrocenyl exhibits higher ability to inhibit DNA oxidation than hydroxyl group.Twenty-two 2-phenyl-4-ferrocenylquinolines are synthesized by Povarov three-component-reaction (3CR) among the substituted anilines, benzaldehydes, and ferrocenylacetylene with Ce(OTf)3 being catalyst in the absence of solvents. The antioxidative effects of the obtained quinolines are estimated by quenching 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and galvinoxyl radicals, and by inhibiting Cu2+/glutathione (GSH)-, hydroxyl radical (OH)–, and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidations of DNA. It is found that the ferrocenyl group instead of hydroxyl group generates the antioxidative effect for quinoline to quench radicals and to protect DNA against radical-induced oxidations. The antioxidative effect generated by ferrocenyl group can be further increased by the electron-donating moieties such as furan, –N(CH3)2, –OCH3, and ferrocenyl group, while the electron-withdrawing groups such as –NO2 and –Cl are not beneficial for quinolines to be antioxidants. The ferrocenyl group in quinoline exhibits higher antioxidant activity than hydroxyl group in Trolox.The ferrocenyl group instead of hydroxyl group makes quinoline an antioxidant to inhibit DNA oxidation and to scavenge radicals.
Co-reporter:Hai-Wang Lai, Zai-Qun Liu
European Journal of Medicinal Chemistry 2014 Volume 81() pp:227-236
Publication Date(Web):23 June 2014
DOI:10.1016/j.ejmech.2014.04.081
•Thirteen thiaflavans were synthesized.•Effects of these thiaflavans on scavenging radicals and inhibiting DNA oxidation were compared.•Ferrocene-appended thiaflavans exhibited the highest antioxidant activity.4-Thiaflavan is a sulfur-substituted flavonoid with a benzoxathiin scaffold. The aim of this work is to compare abilities of sulfur and oxygen atom, hydroxyl groups, and ferrocene moiety at different positions of 4-thiaflavan to trap radicals and to inhibit DNA oxidation. It is found that abilities of thiaflavans to trap radicals and to inhibit DNA oxidation are increased in the presence of ferrocene moiety and are further improved by the electron-donating group attaching to thiaflavan skeleton. It can be concluded that the ferrocene moiety plays the major role for thiaflavans to be antioxidants even in the absence of phenolic hydroxyl groups. On the other hand, the antioxidant effectiveness of phenolic hydroxyl groups in thiaflavans can be improved by the electron-donating group. The influences of sulfur and oxygen atoms in thiaflavans on the antioxidant property of para-hydroxyl group exhibit different manners when the thiaflavans are used to trap radicals and to inhibit DNA oxidation.Thirteen thiaflavans were synthesized and effects of these thiaflavans on scavenging radicals and inhibiting DNA oxidation were compared. Ferrocene-appended thiaflavans exhibited the highest antioxidant activity.
Co-reporter:Gao-Lei Xi and Zai-Qun Liu
Journal of Agricultural and Food Chemistry 2014 Volume 62(Issue 24) pp:5636-5642
Publication Date(Web):June 9, 2014
DOI:10.1021/jf500013v
Coumestan is a natural tetracycle with a C═C bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS•+), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by •OH, Cu2+/glutathione (GSH), and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit •OH-, Cu2+/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit •OH- and Cu2+/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant.
Co-reporter:Gao-Lei Xi, Zai-Qun Liu
Tetrahedron 2014 70(44) pp: 8397-8404
Publication Date(Web):
DOI:10.1016/j.tet.2014.08.063
Co-reporter:Pei-Ze Li
Medicinal Chemistry Research 2014 Volume 23( Issue 7) pp:3478-3490
Publication Date(Web):2014 July
DOI:10.1007/s00044-014-0924-1
A series of asymmetrical mono-carbonyl ferrocenylidene curcumin and their dihydropyrazole derivatives were synthesized. Their antioxidant abilities in protecting DNA against 2,2′-azobis(2-amidinopropane hydrochloride)-induced oxidation and scavenging 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS) radical were evaluated. In synthesis, the Michael addition reactions between phenylhydrazine and asymmetrical ferrocenylidene curcumin derivatives exhibit evident regioselectivity. The direction of addition depends on whether the benzene ring is substituted or not. The antioxidant abilities of compounds will increase when the ferrocenyl group is introduced. Moreover, such improvement derived from ferrocenyl group is also related to other substituent groups in molecule, not independent. Interestingly, p-dimethylamino group which is never considered as an active group, however, exhibits the best activity in protecting DNA and scavenging ABTS radical.
Co-reporter:Yan-feng Li
Chemical Research in Chinese Universities 2013 Volume 29( Issue 4) pp:671-677
Publication Date(Web):2013 August
DOI:10.1007/s40242-013-3059-x
Effects of 4-(1,3-diphenyl-1H-pyrazol-5-yl)phenol(APP), 4-(1,5-diphenyl-1H-pyrazol-3-yl)phenol(BPP) and 4-(3,5-diphenyl-1H-pyrazol-1-yl)phenol(CPP) on 2,2′-azobis-(2-amidinopropane hydrochloride)(AAPH)-induced oxidation of DNA were measured in the presence of various concentrations of Triton X-100, cetyltrimethylammonium bromide(CTAB), or sodium dodecyl sulfate(SDS) in order to clarify the influence of neutral, cationic and anionic microenvironments on antioxidant capacities of APP, BPP and CPP. Although these surfactants can protect DNA against AAPH-induced oxidation, the pyrazoles in the presence of these surfactants functioned as prooxidants when the concentrations of Triton X-100 and CTAB increased. However, CPP exhibited antioxidant property with the increase of the concentration of CTAB. On the contrary, APP, BPP and CPP were antioxidants in the presence of various concentrations of SDS. The added surfactants resulted in the complication of the microenvironments around DNA, pyrazoles and peroxyl radical(ROO·) derived from AAPH. The anionic charge of SDS was beneficial to enhancing the antioxidant effectiveness of these pyrazoles. It can be concluded that the charge property of surfactants markedly influenced the behavior of an antioxidant in AAPH-induced oxidation of DNA.
Co-reporter:Pei-Ze Li, Zai-Qun Liu
Tetrahedron 2013 69(46) pp: 9898-9905
Publication Date(Web):
DOI:10.1016/j.tet.2013.08.053
Co-reporter:Rui Wang and Zai-Qun Liu
The Journal of Organic Chemistry 2013 Volume 78(Issue 17) pp:8696-8704
Publication Date(Web):August 23, 2013
DOI:10.1021/jo401426n
The hydroxyl-substituted benzoic acid (as phenyl group A in the product), aniline (as phenyl group B in the product), benzaldehyde (as phenyl group C in the product), and four isocyanides are employed to synthesize bis-amide via an Ugi four-component reaction. The effects of the obtained 20 bis-amides on quenching radicals and inhibiting DNA oxidation are estimated. It is found that the antioxidant effectiveness of bis-amide generated by hydroxyl groups is markedly influenced by the structural feature derived from isocyanide. The phenolic hydroxyl group attaching to phenyl group A plays a major role in scavenging radicals, and the radical-scavenging property is reinforced by the structural moiety introduced from ferrocenylmethyl isocyanide. The same conclusion is also obtained when bis-amides are used to inhibit DNA oxidation. It is still found that the ferrocenylmethyl moiety enhances the antioxidant effect of hydroxyl group at phenyl group A in protecting DNA against the oxidation. Moreover, when the bis-amide is prepared by the same isocyanide, e.g. ethyl isocyanoacetate, it is found that the hydroxyl group at phenyl group C plays the major role in inhibiting DNA oxidation, followed by the hydroxyl groups attaching to phenyl groups B and A.
Co-reporter:Rui Wang
Medicinal Chemistry Research 2013 Volume 22( Issue 4) pp:1563-1569
Publication Date(Web):2013 April
DOI:10.1007/s00044-012-0157-0
The aim of this work was to clarify the influences of the position of hydroxyl group and furo[2,3-b] moiety on the antioxidant effectiveness of quinoline. Thus, 4-methyl-2,3-dihydrofuro[2,3-b]quinolin-6-ol (PFQ), 4-methyl-2,3-dihydrofuro[2,3-b]quinolin-8-ol (OFQ), and 4-methyl-2,3-dihydrofuro[2,3-b]quinolin-7-ol (MFQ) were synthesized by a recyclization reaction of 1-acetyl-N-phenylcyclopropanecarboxamide in the presence of SnCl4 as the catalyst. The antioxidant capacities of PFQ, OFQ, and MFQ were evaluated in the experimental system of the oxidation of DNA caused by Cu2+/glutathione (GSH), •OH, and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). OFQ and PFQ were able to protect DNA against Cu2+/GSH- and •OH-induced oxidation because the furo[2,3-b] moiety was beneficial for stabilizing the produced furoquinoline radical. Moreover, MFQ can decrease the oxidation rate of AAPH-induced oxidation of DNA, while PFQ and OFQ can inhibit AAPH-induced oxidation of DNA for a period. The data obtained from AAPH-induced oxidation of DNA were treated by chemical kinetic method; it was found that PFQ and OFQ can trap 1.3 and 1.5 radicals, respectively. Therefore, the hydroxyl group at different positions changed the mechanism of furoquinoline in protecting DNA against radical-induced oxidation.
Co-reporter:GUL NABI
Journal of Food Biochemistry 2012 Volume 36( Issue 1) pp:38-45
Publication Date(Web):
DOI:10.1111/j.1745-4514.2010.00501.x
ABSTRACT
This work dealt with the influence of the position of hydroxyl on the antioxidant capacity of metabolites of chlorogenic acid involving ferulic acid (FA), m- and p-coumaric acid (m- and p-CA). They were applied to protect DNA against the oxidations mediated by Cu2+/glutathione (GSH) and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). FA, m- and p-CA were also employed to inhibit the autoxidation of linoleic acid and AAPH-induced oxidation of methyl linoleate. Finally, they were used to scavenge 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+•), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and galvinoxyl radicals. It was found that FA, m- and p-CA exhibited similar activities to protect DNA against Cu2+/GSH-induced oxidation and to interact with ABTS+• m-CA exhibited low activity in AAPH-induced oxidations of DNA and methyl linoleate whereas p-CA exhibited high activity. FA exhibited much higher activity to trap DPPH and galvinoxyl radicals, revealing that para-hydroxyl group, especially with an adjacent methoxyl group, was beneficial for the antioxidant activity of coumaric acid.
PRACTICAL APPLICATIONS
The antioxidant effectiveness of ferulic acid, m- and p-coumaric acid in trapping radicals and protecting methyl linoleate and DNA against radical-induced oxidations has been investigated in this work. It was found that antioxidant activities of these compounds were composed of radical-reducing and radical-scavenging aspects. The hydroxyl adjacent to methoxyl is beneficial to scavenging radicals whereas hydroxyl at any position can play a radical-reducing role. The result presented herein will lead to a detailed recognition for the antioxidant mechanism of coumaric acid.
Co-reporter:Rui Wang and Zai-Qun Liu
The Journal of Organic Chemistry 2012 Volume 77(Issue 8) pp:3952-3958
Publication Date(Web):April 10, 2012
DOI:10.1021/jo300282y
Benzoyl and ferrocenoyl 3,4-dihydropyrimidin-2(1H)-ones (-thiones) (DHPMs) were synthesized in modest yields via catalyst-free and solvent-free Biginelli condensation of 1-phenylbutane-1,3-dione or 1-ferrocenylbutane-1,3-dione, hydroxyl benzaldehyde, and urea or thiourea. This synthetic protocol revealed that catalysts may not be necessary for the self-assembling Biginelli reaction. The radical-scavenging abilities of the obtained 11 DHPMs were carried out by reacting with 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+•), galvinoxyl radical, and 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), respectively. The variation of the concentration of these radicals with the reaction time (t) followed exponential function, [radical] = Ae–t/a + Be–t/b + C. Then, the differential style of this equation led to the relationship between the reaction rate (r) and the reaction time (t), –d[radical]/dt = (A/a)e–t/a + (B/b)e–t/b, which can be used to calculate the reaction rate at any time point. On the basis of the concept of the reaction rate, r = k[radical][antioxidant], the rate constant (k) can be calculated with the time point being t = 0. By the comparison of k of DHPMs, it can be concluded that phenolic ortho-dihydroxyl groups markedly enhanced the abilities of DHPMs to quench ABTS+•, but the introduction of ferrocenoyl group made DHPMs efficient ABTS+• scavengers even in the absence of phenolic hydroxyl group. This phenomenon was also found in DHPM-scavenging galvinoxyl radical. In contrast, the ferrocenoyl group cannot enhance the abilities of DHPMs to scavenge DPPH, and phenolic ortho-dihydroxyl groups still played the key role in this case.
Co-reporter:Pei-Ze Li, Zai-Qun Liu
European Journal of Medicinal Chemistry 2011 Volume 46(Issue 5) pp:1821-1826
Publication Date(Web):May 2011
DOI:10.1016/j.ejmech.2011.02.041
The antioxidant capacities of ferrocenyl-substituted curcumin derivatives including 1,7-bis(p-hydroxy-m-methoxyphenyl)-4-ferrocenylidene-hepta-1,6-diene-3,5-dione (FCU), 1-(p-hydroxy-m-methoxyphenyl)-3-hydroxy-7-ferrocenyl-hepta-1,4,6-trien-5-one (FFT), and 1-(p-hydroxy-m-methoxyphenyl)-5-ferrocenyl-penta-1,4-dien-3-one (FDZ) were evaluated in 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), Cu2+/glutathione (GSH), and hydroxyl radical (OH)-induced oxidation of DNA, and in trapping 2,2′-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), and galvinoxyl radicals. FCU, FFT, and FDZ protected DNA against Cu2+/GSH-induced oxidation, but promoted OH-induced oxidation of DNA. FCU, FFT, and FDZ scavenged 9.5, 5.7, and 4.7 radicals in protecting DNA against AAPH-induced oxidation. FCU can trap more DPPH and ABTS+ than FDZ and FFT, whereas FCU, FFT, and FDZ cannot react with galvinoxyl radical. Both phenolic hydroxyl groups and iron atom in ferrocenylidene curcumin derivatives play antioxidant role in this case.Effects of ferrocenylidene curcumin derivatives on Cu2+/GSH, OH, and AAPH-induced oxidation of DNA and on trapping DPPH, ABTS+, and galvinoxyl radical.Highlights► The properties of ferrocenyl curcumins were evaluated in protecting DNA and scavenging radicals. ► The numbers of radicals trapped by ferrocenyl curcumins in the oxidation of DNA were measured. ► Ferrocenyl curcumins act as prooxidants in Cu2+/GSH-induced oxidation of DNA. ► Ferrocenyl curcumins can trap ABTS+ and DPPH radicals, but cannot trap galvinoxyl radical.
Co-reporter:Jian-Ying Feng, Zai-Qun Liu
European Journal of Medicinal Chemistry 2011 Volume 46(Issue 4) pp:1198-1206
Publication Date(Web):April 2011
DOI:10.1016/j.ejmech.2011.01.039
In order to clarify the contribution of phenolic and enolic hydroxyl group to the antioxidant capacity of feruloylacetone, a model compound of half-curcumin, 6-(p-hydroxy-m-methoxyphenyl)-5-hexene-2,4-dione (FT), 6-(p-benzyloxy-m-methoxyphenyl)-5-hexene-2,4-dione (BMFT), 6-(m,p-dihydroxyphenyl)-5-hexene-2,4-dione (DDFT), 6-(p-hydroxy-m-methoxyphenyl)hexane-2,4-dione (DHFT), 6-(p-hydroxy-m-methoxyphenyl)-5-hexene-2,4-diol (THFT), and ethyl 2-(p-hydroxy-m-methoxybenzylidene)-3-oxobutanoate (EOFT) were synthesized. The radical-scavenging abilities of these compounds were tested by trapping 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), 2,2′-diphenyl-1-picrylhydrazyl (DPPH), and galvinoxyl radicals. The reductive capacities were screened by quenching singlet oxygen and by inhibiting the oxidation of linoleic acid. They were also employed to inhibit the oxidation of DNA mediated by hydroxyl radical and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). In addition, they were applied to protect erythrocytes against AAPH- and hemin-induced hemolysis. The obtained results revealed that the antioxidant capacity of half-curcumin was derived from the phenolic-OH and the conjugated linkage between phenolic and enolic-OH. The enolic-OH itself cannot trap radicals.Half-curcumin and its derivatives scavenge radicals, reduce oxidants, and protect DNA and erythrocytes.Research highlights► Half-curcumin derivatives scavenge radicals, reduce oxidants, and protect DNA and erythrocytes. ► Phenolic hydroxyl scavenges radicals effectively, but enolic hydroxyl cannot. ► Half-curcumin derivatives act as prooxidant in Cu2+/GSH-induce oxidation of DNA. ► More phenolic hydroxyls enhance the antioxidant ability to protect DNA and erythrocytes.
Co-reporter:Gul Nabi, Zai-Qun Liu
Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 3) pp:944-946
Publication Date(Web):1 February 2011
DOI:10.1016/j.bmcl.2010.12.051
The radical-scavenging capacities of ferrocenyl group and phenolic hydroxyl group in ferrocenyl chalcone were identified in this work. 1,1′-Diacetylferrocene was applied to condense with benzaldehyde, vanillin, and protocatechualdehyde to produce ferrocenyl chalcones, which were employed to interact with 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. It was found that ferrocenyl chalcones as well as diacetylferrocene can trap these radicals effectively, and thus, concluded that both iron atom in ferrocene and phenolic hydroxyl group played the radical-scavenging role, and the radical-scavenging capacity of iron atom in ferrocene was even higher than that of phenolic hydroxyl group.ABTS+, DPPH, and galvinoxyl radical-scavenging evaluations revealed that both Fe(II) in ferrocene and hydroxyl groups in ferrocenyl chalcones played radical-scavenging role.
Co-reporter:Feng Zhao
Journal of Biochemical and Molecular Toxicology 2011 Volume 25( Issue 4) pp:216-223
Publication Date(Web):
DOI:10.1002/jbt.20378
Abstract
The abilities of dihydrolipoic acid (DHLA) to scavenge peroxynitrite (ONOO−), galvinoxyl radical, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS+•), and 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) were higher than those of lipoic acid (LA). The effectiveness of DHLA to protect methyl linoleate against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation was about 2.2-fold higher than that of LA, and DHLA can retard the autoxidation of linoleic acid (LH) in the β-carotene-bleaching test. DHLA can also trap ∼0.6 radicals in AAPH-induced oxidation of LH. Moreover, DHLA can scavenge ∼2.0 radicals in AAPH-induced oxidation of DNA and AAPH-induced hemolysis of erythrocytes, whereas LA can scavenge ∼1.5 radicals at the same experimental conditions. DHLA can protect erythrocytes against hemin-induced hemolysis, but accelerate the degradation of DNA in the presence of Cu2+. Therefore, the antioxidant capacity of –SH in DHLA is higher than S-S in LA. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:216–223, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20378
Co-reporter:Feng Zhao;Chao Zhao
JBIC Journal of Biological Inorganic Chemistry 2011 Volume 16( Issue 8) pp:1169-1176
Publication Date(Web):2011 December
DOI:10.1007/s00775-011-0805-8
The aim of this work was to clarify the effect of the position of the hydroxyl group on the antioxidant capacity of hydroxyferrocifen by means of a chemical kinetic method. Propionylferrocene and benzoylferrocene condensed with 4-hydroxydiphenylketone, 3,4-dihydroxydiphenylketone, and 4,4′-dihydroxydiphenylketone to form FP3, FP4, FB3, and FB4 with a single hydroxyl group and FP34, FP44, FB34, and FB44 with two hydroxyl groups. These hydroxyferrocifens were applied in Cu2+/glutathione (GSH)-induced, hydroxyl radical (·OH)-induced, and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA, and in trapping 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+·). It was found that these hydroxyferrocifens acted as prooxidants in Cu2+/GSH-induced oxidation of DNA and exhibited very weak effects on ·OH-induced oxidation of DNA. FP3, FP4, FB3, and FB4 can only retard the rate of AAPH-induced oxidation of DNA, whereas FP44, FB44, FB34, and FP34 can trap 11.9, 7.1, 6.2, and 4.9 radicals, respectively, in AAPH-induced oxidation of DNA. The ability to trap ABTS+· followed the order FB4 > FP44 > FB34 > FB44 > FP34. It was concluded that two hydroxyl groups at the para position of two benzene rings rather than at the ortho position in the same benzene ring were beneficial for hydroxyferrocifen to increase the antioxidant capacity.
Co-reporter:Zai-Qun Liu
Chemical Reviews 2010 Volume 110(Issue 10) pp:5675
Publication Date(Web):July 12, 2010
DOI:10.1021/cr900302x
Co-reporter:Guo-Xiang Li, Zai-Qun Liu, Xu-Yang Luo
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 5) pp:1821-1827
Publication Date(Web):May 2010
DOI:10.1016/j.ejmech.2010.01.018
5,7-, 5,8-, 6,8-, 7,8-Dichloro-4-quinolinol-3-carboxylic acid (5,7-, 5,8-, 6,8-, 7,8-DCQA) together with 7-chloro-4-quinolinol-3-carboxylic acid (7-CQA) and 4-quinolinol-3-carboxylic acid (QA) were synthesized to investigate the antioxidant properties. 5,7-DCQA exhibited the highest ability to scavenge 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+.), 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and galvinoxyl radicals. 6,8-DCQA possessed the highest efficacy to protect methyl linoleate against 2,2′-azobis(2-amidinopropane)dihydrochloride (AAPH)-induced oxidation. 5,7-, 5,8-DCQA and QA were able to retard the β-carotene-bleaching in β-carotene-linoleic acid emulsion. In addition, 5,8- and 6,8-DCQA efficiently protected DNA against hydroxyl radical (.OH)-mediated oxidation, and 5,8-DCQA and 7-CQA were active to protect DNA against AAPH-induced oxidation. Furthermore, only 7-CQA can protect DNA against Cu2+/glutathione (GSH)-mediated oxidation. Dichloro-4-quinolinol-3-carboxylic acids were potent to be antiradical drugs, and were worthy to be researched pharmacologically.4-Quinolinols were applied to trap ABTS+., DPPH and galvinoxyl radicals, to inhibit radical-induced oxidation of methyl linoleate, and to protect DNA against hydroxyl, peroxyl radicals, and Cu2+/glutathione-mediated oxidation.
Co-reporter:Chuan Xiao, Zhi-Guang Song, Zai-Qun Liu
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 6) pp:2559-2566
Publication Date(Web):June 2010
DOI:10.1016/j.ejmech.2010.02.044
4-Methyl-8-hydroxylpsoralen (MXan) and 4,9-dimethyl-8-hydroxylpsoralen (DMXan) were synthesized in order to clarify the effect of methyl on the antioxidant effectiveness of xanthotoxol (8-hydroxylpsoralen, Xan), which were assessed by bleaching β-carotene in linoleic acid–Triton emulsion, by interacting with 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, and by protecting DNA against the oxidation induced by Cu2+/glutathione (GSH) and 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). Methyl attaching to xanthotoxol did not affect its ability to protect linoleic acid against autoxidation and to inhibit Cu2+/GSH-induced oxidation DNA, but decreased its ability to scavenge ABTS+ and DPPH, and to protect DNA against AAPH-induced oxidation. Therefore, methyl attenuated the antioxidant effectiveness of xanthotoxol in radical-induced oxidation of DNA.Detect the antioxidant effects of Xan, MXan and DMXan on the oxidation of DNA induced by Cu2+/glutathione and peroxyl radical to clarify that methyl attenuated the antioxidant capacity of Xan.
Co-reporter:Yan-Feng Li, Zai-Qun Liu and Xu-Yang Luo
Journal of Agricultural and Food Chemistry 2010 Volume 58(Issue 7) pp:4126-4131
Publication Date(Web):March 3, 2010
DOI:10.1021/jf904089q
3-(2′-, 3′-, and 4′-Hydroxybenzylidene)-7-methoxychroman-4-one (o-, m-, and p-HBMC) was synthesized for the clarification of the influence of the hydroxyl group at the B ring on the antioxidant activity of homoisoflavonoid. The three homoisoflavonoids used herein can reduce peroxynitrite. p-HBMC exhibited high activity to reduce singlet oxygen. Furthermore, o-, m-, and p-HBMC can scavenge the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS•+) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and galvinoxyl radicals. The rates of o-HBMC trapping of DPPH and galvinoxyl radicals were higher than those of m- and p-HBMC, whereas m-HBMC can trap ABTS•+ rapidly. o-HBMC was found to possess high activity in the β-carotene−linoleic acid bleaching test and to protect methyl linoleate against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation efficiently. Finally, o-HBMC served as a prooxidant in Cu2+/glutathione (GSH)- and hydroxyl radical-mediated oxidations of DNA. m- and p-HBMC protected DNA against hydroxyl radical-mediated oxidation of DNA effectively, and o- and p-HBMC behaved as antioxidants to protect DNA against AAPH-induced oxidation. Thus, the hydroxyl group attaching to the ortho- and para-positions in the B ring was of importance for the homoisoflavonoid's enhancement of antioxidant activity.
Co-reporter:Guo-Xiang Li, Zai-Qun Liu
European Journal of Medicinal Chemistry 2009 Volume 44(Issue 12) pp:4841-4847
Publication Date(Web):December 2009
DOI:10.1016/j.ejmech.2009.07.020
Antioxidant capacities of captopril (CAP), 6-mercaptopurine (6-MP) and 9-(β-d-ribofuranosyl)-6-mercaptopurine (6-MPR) were investigated by interacting them with 2,2′-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical, and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS+), and by protecting DNA and erythrocyte against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) induced oxidation. It was found that CAP possessed the highest ability to donate the hydrogen atom in –SH to DPPH and galvinoxyl, while 6-MPR had the strongest ability to reduce ABTS+. In the process of protecting DNA and erythrocytes against AAPH-induced oxidation, CAP can trap 0.5 and 1.3 radicals, 6-MP can trap 0.6 and 2.2, and 6-MPR can trap 1.0 and 3.0 radicals, respectively. CAP can also protect erythrocytes against hemin-induced hemolysis.Antioxidant properties of captopril, 6-mercaptopurine and 9-(β-d-ribofuranosyl)-6-mercaptopurine were screened by protecting DNA and erythrocytes, and by interacting with radicals. The –SH group attached to aromatic ring possessed high antioxidant effectiveness.
Co-reporter:Guo-Xiang Li and Zai-Qun Liu
Journal of Agricultural and Food Chemistry 2009 Volume 57(Issue 9) pp:3943-3948
Publication Date(Web):March 27, 2009
DOI:10.1021/jf803358g
The antioxidant effects of α-terpinene (α-TH) and γ-terpinene (γ-TH) on the oxidation of methyl linoleate (LH), DNA, and erythrocytes induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) were investigated. The results from erythrocytes and DNA were treated by means of chemical kinetic equations. It was found that either α- or γ-TH was able to scavenge ∼0.4 radicals when they protected DNA. α-TH can trap ∼0.7 radicals when protecting erythrocytes and can trap ∼0.5 radicals when protecting LH. γ-TH can trap ∼1.2 radicals when protecting erythrocytes and LH. Therefore, the antioxidant effectiveness of γ-TH was higher than α-TH. γ-TH contained a nonconjugated diene, and the diene in α-TH was conjugated. The obtained results implied that the nonconjugated diene benefited for antioxidant capacity more than a conjugated diene. Moreover, the reactions of α- and γ-TH with 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS+ •) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) implicated that α- and γ-TH were able to scavenge radicals directly. However, α- and γ-TH promoted AAPH-induced hemolysis with a high concentration employed.
Co-reporter:Jian-Ying Feng and Zai-Qun Liu
Journal of Agricultural and Food Chemistry 2009 Volume 57(Issue 22) pp:11041-11046
Publication Date(Web):September 8, 2009
DOI:10.1021/jf902244g
The aim of this work is to clarify the antioxidant abilities of phenolic and enolic hydroxyl groups in curcumin. 1,7-Bis(4-benzyloxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (BEC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol (OHC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (THC), and 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (BDC) are synthesized to determine the antioxidant activities by using antiradical assays against 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical, galvinoxyl radical, and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS•+) and by protecting DNA and erythrocyte against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) induced oxidation. The phenolic hydroxyl is the main group for curcumin to trap DPPH, galvinoxyl, and ABTS•+ radicals. The conjugative system between enolic and phenolic hydroxyl groups is beneficial for curcumin to protect erythrocytes against hemin-induced hemolysis and to protect DNA against AAPH-induced oxidation, but is not beneficial for curcumin to protect erythrocytes against AAPH-induced hemolysis. More hydroxyl groups enhance the antioxidant effectiveness of curcumin in the experimental systems employed herein. Therefore, curcumin acts as an antioxidant through the phenolic hydroxyl group.
Co-reporter:You-Zhi Tang;Di Wu
Journal of Biochemical and Molecular Toxicology 2009 Volume 23( Issue 2) pp:81-86
Publication Date(Web):
DOI:10.1002/jbt.20267
Abstract
Lidocaine was reported to protect erythrocytes from hemolysis induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). Since AAPH-induced hemolysis was a convenient in vitro experimental system to mimic erythrocytes undergoing peroxyl radicals attack, the aim of this work was to investigate the antioxidant effect of lidocaine on AAPH-induced hemolysis by chemical kinetics. As a result, one molecule of lidocaine can only trap 0.37 radical, much lower than melatonin. Meanwhile, lidocaine cannot protect erythrocytes from hemolysis induced by hemin, which the mechanism of hemolysis was due to the erythrocyte membrane destroyed by hemin. Accordingly, lidocaine protected erythrocytes by scavenging radicals preferentially rather than by stabilizing membrane. Moreover, the interactions of lidocaine with two radical species, including 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS+•) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH), indicated that lidocaine can reduce ABTS+• with 260 µM as the 50% inhibition concentration (IC50) and cannot react with DPPH. Thus, lidocaine served as a reductant rather than a hydrogen donor to interact with radicals. Finally, the quantum calculation proved that, compared with the melatonin radical, the stabilization of N-centered radical of lidocaine was higher than the amide-type N-centered radical but lower than the indole-type N-centered radical in melatonin. These results provided basic information for lidocaine to be an antiradical drug. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:81–86, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20267
Co-reporter:Guo-Xiang Li;You-Zhi Tang
Journal of Biochemical and Molecular Toxicology 2009 Volume 23( Issue 4) pp:280-286
Publication Date(Web):
DOI:10.1002/jbt.20290
Abstract
Phenothiazine (PtzNH) and phenoxazine (PozNH) can protect human erythrocytes against hemolysis induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), a peroxyl radical supplier. However, an antioxidant may be a pro-oxidant to accelerate the oxidation in the presence of radicals. The aim of this work is to assess whether PtzNH and PozNH have the potential to be pro-oxidants in AAPH-induced hemolysis of human erythrocytes. It has been found that high concentrations of PtzNH and PozNH employed were able to initiate hemolysis even in the absence of AAPH. In the presence of AAPH, the period of PtzNH and PozNH to lag hemolysis (tlag) decreased with the increase in the concentrations of PtzNH and PozNH, implicating that high concentration of PtzNH and PozNH accelerated hemolysis. So, PtzNH and PozNH played pro-oxidants' role in this case. Furthermore, high concentrations of AAPH employed made the pro-oxidant effect of PtzNH more remarkable. On the contrary, PozNH played a pro-oxidant role if only low concentration of AAPH was employed. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:280–286, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20290
Co-reporter:Feng Zhao
Journal of Biochemical and Molecular Toxicology 2009 Volume 23( Issue 4) pp:273-279
Publication Date(Web):
DOI:10.1002/jbt.20289
Abstract
The antioxidant properties of 1,2,3,4-tetra-hydrocarbazole, 6-methoxy-1,2,3,4-tetrahydrocar-bazole (MTC), 2,3-dimethylindole, 5-methoxy-2,3-dimethylindole, and indole were investigated in the case of hemolysis of human erythrocytes and oxidative damage of DNA induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. The aim of this work was to explore the influence of methoxy, methyl, and cyclohexyl substituents on the antioxidant activities of indole derivatives. These indole derivatives were able to protect erythrocytes and DNA in a concentration-dependent manner. The alkyl-substituted indole can protect erythrocytes and DNA against AAPH-induced oxidation. Especially, the structural features of cyclohexyl and methoxy substituents made MTC the best antioxidant among the indole derivatives used herein. Finally, the interaction between these indole derivatives and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation and 2,2′-diphenyl-1-picrylhydrazyl, respectively, provided direct evidence for these indole derivatives to scavenge radicals and emphasized the importance of electron-donating groups for the free radical–scavenging activity of indole derivatives. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:273–279, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20289
Co-reporter:Zai-Qun Liu;Di Wu
Journal of Physical Organic Chemistry 2009 Volume 22( Issue 4) pp:308-312
Publication Date(Web):
DOI:10.1002/poc.1472
Abstract
Eleven hydroxyl-substituted Schiff bases (SchOHs) were synthesized by the reaction between hydroxyl-substituted benzaldehydes and hydroxyl-substituted anilines, and their antioxidant effects on the oxidation of linoleic acid (dissolved in sodium dodecyl sulfate micelle) induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) were investigated. The relationships between the period of the oxidation inhibited by SchOHs (tinh) and their concentrations ([SchOHs]) were measured firstly, and then treated by a chemical kinetic equation, tinh = (n/Ri)[SchOH], to obtain the number (n) of the oxidative chains terminated by one molecule of SchOH. Therefore, the antioxidant activities of SchOHs can be expressed quantitatively by the n value. Finally, the spin-densities (SD) on O atom in the radical of SchOH (SchO.) were calculated by quantum chemical method, and, to some extent, SD provided an explanation to the difference of the antioxidant effects among various SchOH. Therefore, the obtained results provided an attempt to bridge the kinetic measurement and quantum calculation in the study on the property of an antioxidant. Copyright © 2008 John Wiley & Sons, Ltd.
Co-reporter:Guo-Xiang Li;Di Wu
Journal of Physical Organic Chemistry 2009 Volume 22( Issue 9) pp:883-887
Publication Date(Web):
DOI:10.1002/poc.1536
Abstract
This work explored the antioxidant effect of carminic acid (CarOH) on the oxidation of DNA and erythrocytes induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). The half concentrations (IC50) of CarOH to scavenge radicals were measured by reacting with 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS+•) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH). The values of IC50 were 8.0 and 26.0 µM when CarOH reacted with ABTS+• and DPPH, respectively. CarOH was able to protect DNA against AAPH-induced oxidative damage by decreasing the formation rate of thiobarbituric acid reactive substance (TBARS). In addition, CarOH protected human erythrocytes against AAPH-induced hemolysis concentration dependently, during which one molecule of CarOH can trap almost three radicals. Moreover, quantum calculation revealed that the hydroxyl group at 6-position played major role in trapping radicals. Copyright © 2009 John Wiley & Sons, Ltd.
Co-reporter:Feng Zhao
Journal of Physical Organic Chemistry 2009 Volume 22( Issue 9) pp:791-798
Publication Date(Web):
DOI:10.1002/poc.1517
Abstract
The protective effects of 18 hydroxyl-substituted Schiff bases (SchOHs) on the oxidative damage of naked DNA induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) were reported, in which SchOHs were prepared by condensing hydroxyl-substituted aromatic aldehydes and anilines. The extent of the oxidative damage of DNA was followed by measuring the formation of thiobarbituric acid reactive substance (TBARS). Some SchOHs bearing only one hydroxyl group (prepared by salicylic aldehyde) protected DNA by decreasing the formation rate of TBARS. Other SchOHs inhibited the oxidation of DNA for a period, resulting in an inhibition period (tinh) that was proportional to the concentration of SchOH, viz., tinh = (n/Ri)[SchOH]. Thus, the stoichiometric factor (n) can be calculated if the initiation rate (Ri) was known. The n value of an SchOH was closed to the summation of the n from every structural feature in this SchOH, indicating that the antioxidant activity of SchOH was contributed from every structural feature in the molecule. Furthermore, the large conjugative system and para-hydroxyl at benzilidene were good for the antioxidant activity of SchOHs. Copyright © 2009 John Wiley & Sons, Ltd.
Co-reporter:Zai-Qun Liu;You-Zhi Tang;Di Wu
Journal of Physical Organic Chemistry 2009 Volume 22( Issue 10) pp:1009-1014
Publication Date(Web):
DOI:10.1002/poc.1554
Abstract
Antioxidant effects of phenothiazine (PtzNH), phenoxazine (PozNH), and iminostilbene (IsbNH) on the oxidation of linoleic acid (LH) and DNA induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) were investigated in this work. LH was suspended in the liposome of dipalmitoyl phosphatidylcholine (DPPC) to mimic a biomembrane. In the course of AAPH-induced oxidation of LH, the inhibition period (tinh) generated by PtzNH, PozNH, and IsbNH was proportional to the concentrations of PtzNH, PozNH, and IsbNH employed. The abilities of PtzNH, PozNH, and IsbNH to protect LH were similar to that of trolox (6-hydroxyl-2,5,7,8-tetramethylchroman-2-carboxylic acid). Quantum chemical calculations elucidated that the nonplanar configurations of PtzNH, PozNH, and IsbNH transformed to planar ones when they were converted into radicals. In addition, spin-densities (SDs) on the N atom in the radicals derived from PtzNH, PozNH, and IsbNH were calculated. The N atom in the radical of PtzNH possessed the lowest SD, indicating that the radical of PtzNH was the most stable one. Moreover, PtzNH, PozNH, and IsbNH were applied to protect the DNA against AAPH-induced oxidation, in which PozNH and IsbNH were able to generate tinh. The tinh generated from PozNH and IsbNH was also proportional to their concentrations. The antioxidant effect of PozNH on the oxidation of DNA was higher than that of IsbNH. Copyright © 2009 John Wiley & Sons, Ltd.
Co-reporter:You-Zhi Tang and Zai-Qun Liu
Journal of Agricultural and Food Chemistry 2008 Volume 56(Issue 22) pp:11025-11029
Publication Date(Web):November 4, 2008
DOI:10.1021/jf802462h
As an abundant ingredient in coffee, chlorogenic acid (CGA) is a well-known antioxidant. Although some works have dealt with its radical-scavenging property, the present work investigated the protective effects of CGA on the oxidation of DNA and on the hemolysis of human erythrocytes induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH) by means of chemical kinetics. The inhibition period (tinh) derived from the protective effect of CGA on erythrocyte and DNA was proportional to its concentration, tinh = (n/Ri)[CGA], where Ri refers to the radical-initiation rate, and n indicates the number of radical-propagation chains terminated by CGA. It was found that the n of CGA to protect erythrocytes was 0.77, lower than that of vitamin E (2.0), but higher than that of vitamin C (0.19). Furthermore, CGA facilitated a mutual protective effect with VE and VC on AAPH-induced hemolysis by increasing n of VE and VC. CGA was also found to be a membrane-stabilizer to protect erythrocytes against hemin-induced hemolysis. Moreover, the n of CGA was only 0.41 in the process of protecting DNA. This fact revealed that CGA served as an efficient antioxidant to protect erythrocytes more than to protect DNA. Finally, the reaction between CGA and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS+•) or 2,2′-diphenyl-1-picrylhydrazyl (DPPH) revealed that CGA was able to trap radicals by reducing radicals more than by donating its hydrogen atoms to radicals.
Co-reporter:Feng Zhao, Zai-Qun Liu, Di Wu
Chemistry and Physics of Lipids 2008 Volume 151(Issue 2) pp:77-84
Publication Date(Web):February 2008
DOI:10.1016/j.chemphyslip.2007.10.002
The aim of this work is to investigate the antioxidative effect of melatonin (N-acetyl-5-methoxytryptamine) on the oxidation of DNA and human erythrocytes induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). First, the 50% inhibition concentration (IC50) of melatonin is measured by reacting with two radical species, i.e., 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS+) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH). The IC50 of melatonin are 75 μM and 300 μM when melatonin reacts with ABTS+ and DPPH, respectively. Especially, the reactions of melatonin with ABTS+ and DPPH are the direct evidence for melatonin to trap radicals. Then, melatonin is applied to protect DNA and human erythrocytes against oxidative damage and hemolysis induced by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). The presence of melatonin prolongs the occurrence of the oxidative damage of DNA and hemolysis of erythrocytes, generating an inhibition period (tinh). The proportional relationship between tinh and the concentration of melatonin ([MLT]) is treated by the chemical kinetic equation, tinh = (n/Ri)[MLT], in which n means the number of peroxyl radical trapped by an antioxidant, and Ri stands for the initiation rate of the radical reaction. It is found that every molecule of melatonin can trap almost two radicals in protecting DNA and erythrocytes. Furthermore, quantum calculation proves that the indole-type radical derived from melatonin is much stable than amide-type radical. Finally, melatonin is able to accelerate hemolysis of erythrocytes induced by hemin, indicating that melatonin leads to the collapse of the erythrocyte membrane in the presence of hemin. This may provide detailed information for the usage of melatonin and helpful reference for the design of indole-related drugs.
Co-reporter:You-Zhi Tang
Journal of the American Oil Chemists' Society 2007 Volume 84( Issue 12) pp:1095-1100
Publication Date(Web):2007 December
DOI:10.1007/s11746-007-1149-y
Co-reporter:Zai-Qun Liu
Journal of Physical Organic Chemistry 2006 Volume 19(Issue 2) pp:136-142
Publication Date(Web):3 JAN 2006
DOI:10.1002/poc.1011
Vitamin C (L-ascorbic acid) protects human health by scavenging toxic free radicals and other reactive oxygen species formed in cell metabolism. The surplus supplementation of vitamin C, however, may be harmful to health because the level of 8-oxoguanine and 8-oxoadenine in lymphocyte DNA varies remarkably. In the process of the kinetic investigation on the 2,2′-azobis(2-amidinopropane dihydrochloride) (AAPH)-induced autoxidation of glycerol trioleate (GtH) in the micelles of cetyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS) and Triton X-100, the addition of vitamin C accelerates the autoxidation of GtH even in the absence of the free radical initiator, AAPH. The initiating rate, Ri, of vitamin C (VC)-induced autoxidation of GtH is related to the micelle charge, i.e. Ri = 14.4 × 10−6 [VC] s−1 in SDS (anionic micelle), Ri = 1961 × 10−6 [VC] s−1 in Triton X-100 (neutral micelle) and Ri is a maximum in CTAB (cationic micelle) when the vitamin C concentration is ∼300 µM. Thus, vitamin C can initiate autoxidation of GtH in micelles, especially in the neutral one. Moreover, the attempt to explore whether α-tocopherol (TocH) could rectify vitamin C-induced autoxidation of GtH leads us to find that the rate constant of TocH reacting with the anionic radical of vitamin C (VC.−), k−inh, is ∼103M−1 s−1, which is less than that of the α-tocopherol radical (Toc.) with vitamin C (kinh = ∼105 M−1 s−1). Thus, the equilibrium constant of the reaction Toc.+VC−⇌TocH+VC.− is prone strongly to the regeneration of Toc. by vitamin C rather than the reverse reaction. Copyright © 2006 John Wiley & Sons, Ltd.
Co-reporter:Yan-Feng Li, Zai-Qun Liu
European Journal of Pharmaceutical Sciences (18 September 2011) Volume 44(Issues 1–2) pp:158-163
Publication Date(Web):18 September 2011
DOI:10.1016/j.ejps.2011.07.001
The antioxidant capacities of ferrocenyl Schiff bases including o-(1-ferrocenylethylideneamino)phenol (OFP), m-(1-ferrocenylethylideneamino)phenol (MFP), and p-(1-ferrocenylethylideneamino)phenol (PFP) were evaluated in 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH), Cu2+/glutathione (GSH), and hydroxyl radical (OH)-induced oxidation of DNA, and in trapping 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS+), respectively. OFP, MFP and PFP possessed similar activities to trap DPPH and ABTS+. All the ferrocenyl Schiff bases employed herein behaved as prooxidants in Cu2+/GSH- and OH-induced oxidation of DNA except that OFP exhibited weak antioxidant activity in OH-induced oxidation of DNA. PFP, OFP and MFP can terminate about 15.2, 11.3, and 9.4 radical-chain-propagations in AAPH-induced oxidation of DNA. Especially, the introduction of ferrocenyl group to Schiff base increased the antioxidant effectiveness more remarkably than benzene-related Schiff bases.Scavenging ABTS+ and DPPH, and behaviors in Gu2+/GSH-, OH-, and AAPH-induced oxidation of DNA.Download full-size image
Co-reporter:Rui Wang and Zai-Qun Liu
Inorganic Chemistry Frontiers 2014 - vol. 1(Issue 7) pp:NaN797-797
Publication Date(Web):2014/07/10
DOI:10.1039/C4QO00150H
Phenyl and ferrocenyl groups are involved in 3,4-dihydropyrimidin-2(1H)-one (-thione) to form eleven dihydropyrimidines (DHPMs) in this work, aiming to explore the effects of the ferrocene moiety, the CS bond, and the phenolic hydroxyl group on the abilities of DHPMs to protect DNA against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation. It is found that the antioxidant abilities of DHPMs containing CS are higher than those of DHPMs containing CO. In addition, the phenolic hydroxyl group and the CS bond show similar effects on the antioxidant capacities of DHPMs. On the other hand, the ferrocenyl group remarkably increases the antioxidant capacities of DHPMs, while the antioxidant effects of ferrocenyl-appended DHPMs are further improved by the CS bond. Therefore, the influence of the functional group on the antioxidant abilities of DHPMs follows the order: ferrocenyl group > CS bond > phenolic hydroxyl group.
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