Xianming Hu

Name:

Organization: Wuhan University

Department: State Key Laboratory of Virology, College of Pharmacy

Title:

Chemicals
References

Cytotoxicity of cationic liposomes coated by N-trimethyl chitosan and their in vivo tumor angiogenesis targeting containing doxorubicin

Co-reporter:Xian-Xi Guo;Wen He;Xiao-Jie Zhang;Xian-Ming Hu

Journal of Applied Polymer Science 2013 Volume 128( Issue 1) pp:21-27

Publication Date(Web):

DOI:10.1002/app.37701

Abstract

Doxorubicin (DOX)-loaded cationic liposomes (DOXL) coated by N-trimethyl chitosan (TMCs) has been previously shown to enhance DOX uptake by human umbilical vein endothelial cells (HUVECs) in vitro and the tumor inhibition on solid tumor in vivo, and the effects were both enhanced with the degree of quaternization (DQ) increase of TMCs. The aim of the present work is to study the cytotoxicity of the blank cationic liposomes (CLs) coated by TMCs with various DQ on L-929 mouse fibroblasts, by MTT assay, using the relative proliferation rate as the indicator, and the toxicity extent was classified according to the evaluation criteria of United States Pharmacopoeia. Furthermore, the in vivo tumor angiogenesis targeting of DOXL coated by TMC60 was studied. It was found that with the increase of TMCs concentration and DQ, cytotoxicity was increased accordingly. However, the cell proliferation rates of TMCs-coated CLs with TMCs concentrations of 0.02% and 0.05%(w/w) were all above 80%, even the concentration of TMC20 was increased to 0.2%(w/w), the cell proliferation rate was still above 80%, showing noncytotoxicity. The mouse H₂₂ tumor model was established by transplanted tumor experiment. In vivo fluorescence in tumor tissue was investigated through the tail vein injection of fluorescein isothiocyanate conjugated dextran at the 7th day after the administration of different DOX preparations. Compared with DOX solution and uncoated DOXL, the mice given TMC60-coated DOXL showed tumor angiogenesis with good shape, uniform arrangement, and small vascular branches, and the vascular density was decreased, suggesting promising tumor angiogenesis targeting of TMC60-coated DOXL. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

An Efficient Route to Quinolines and Other Compounds by Iron-Catalysed Cross-Dehydrogenative Coupling Reactions of Glycine Derivatives

Co-reporter:Peng Liu;Zhiming Wang;Jue Lin

European Journal of Organic Chemistry 2012 Volume 2012( Issue 8) pp:1583-1589

Publication Date(Web):

DOI:10.1002/ejoc.201101656

Abstract

A simple method has been developed for functionalizing glycine derivatives by iron-catalysed cross-dehydrogenative coupling (CDC) reactions. In particular, N-arylglycine derivatives reacted with alkynes by oxidative C–H/C–H coupling reactions to provide a series of substituted quinolines starting from commercially inexpensive materials. Moreover, N-arylglycine esters can be oxidatively coupled to ketones by using FeCl₃ in the presence of DDQ.

Highly Efficient Synthesis of Ureas and Carbamates from Amides by Iodosylbenzene-Induced Hofmann Rearrangement

Co-reporter:Peng Liu;Zhiming Wang

European Journal of Organic Chemistry 2012 Volume 2012( Issue 10) pp:1994-2000

Publication Date(Web):

DOI:10.1002/ejoc.201101784

Abstract

A simple and efficient method for the synthesis of 1,3-disubstituted ureas and carbamates from amides by using iodosylbenzene as the oxidant is described. Symmetric and asymmetric ureas and carbamates can be prepared by this procedure in up to 98 % yield. Ureidopeptides can also be prepared in good yield by this method.

Synthesis and antibacterial activity of 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A: A novel class of acylides

Co-reporter:Zhongyuan Wu, Yong Lu, Ming Luo, Xianran He, Yuling Xiao, Jin Yang, Yuanhu Pan, Guofu Qiu, Hao Guo, Hao Hu, Dingshan Zhou, Xianming Hu

European Journal of Medicinal Chemistry 2010 Volume 45(Issue 9) pp:3636-3644

Publication Date(Web):September 2010

DOI:10.1016/j.ejmech.2010.05.009

A novel series of acylides, 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A, were synthesized and evaluated for their antibacterial activity. These compounds have significant antibacterial activity against Gram-positive pathogens, including erythromycin-resistant but methicillin-susceptible Staphylococcus aureus, erythromycin-resistant and methicillin-resistant S. aureus, erythromycin-resistant Streptococcus pneumoniae, and Gram-negative pathogens, such as Haemophilus influenzae. Among the derivatives tested, compounds 4p, 4r, 4w, 4x and 4z were found to have potent activity against most susceptible and resistant bacteria. Compound 4p exhibited excellent antibacterial activity in comparison to the others.Novel 3-O-carbamate derivatives of 6,11-di-O-methylerythromycin A were synthesized by substituting l-cladinose with various carbamate groups. This new class of antibiotics exhibited potent activity against some key erythromycin-resistant pathogens.

Synthesis and antibacterial activity of novel 4″-carbamates of 6,11-di-O-methylerythromycin A

Co-reporter:Zhongyuan Wu, Yong Lu, Ming Luo, Xianran He, Yuling Xiao, Jin Yang, Yuanhu Pan, Guofu Qiu, Yinya Xu, Wenhong Huang, Ping Long, Ruimin Li and Xianming Hu

The Journal of Antibiotics 2010 63(7) pp:343-350

Publication Date(Web):May 7, 2010

DOI:10.1038/ja.2010.44

A novel series of 4″-carbamates of 6,11-di-O-methylerythromycin A were synthesized and evaluated. These compounds have significant antibacterial activity against Gram-positive pathogens, including erythromycin-resistant but methicillin-susceptible Staphylococcus aureus, erythromycin-resistant and methicillin-resistant Staphylococcus aureus, erythromycin-resistant Streptococcus pneumoniae and Gram-negative pathogens, such as Haemophilus influenzae To our surprise, most of the derivatives tested had potent activity against most resistant bacteria. Among these, compounds 10u, 10v, 10w and 10y were found to have potent activity against most susceptible and resistant bacteria. In particular, compound 10y exhibited excellent antibacterial activity in comparison to others.

Significant steroids: effective and general synthesis of 4α- and 4β-amino-5α-androstanes

Co-reporter:Xianbing Ke, Hao Hu, Keda Zhang, Wenjin Xu, Qifeng Zhu, Lamei Wu and Xianming Hu

Chemical Communications 2009 (Issue 9) pp:1037-1039

Publication Date(Web):27 Jan 2009

DOI:10.1039/B817910G

4α-Aminosteroids were synthesized by the substitution of a 2α-bromo ketone using K2CO3 as an activator; 4β-aminosteroids were synthesized in excellent yields by a highly regioselective and trans-stereospecific ring opening of a steroidal 3,4α-epoxide using ZnCl2–H2O as a catalyst.

Synthesis and potential anticonvulsant activity of new N-3-substituted 5,5-cyclopropanespirohydantoins

Co-reporter:Qifeng Zhu, Yuanhu Pan, Zaixu Xu, Ruimin Li, Guofu Qiu, Wenjin Xu, Xianbing Ke, Lamei Wu, Xianming Hu

European Journal of Medicinal Chemistry 2009 Volume 44(Issue 1) pp:296-302

Publication Date(Web):January 2009

DOI:10.1016/j.ejmech.2008.02.024

Thirteen new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and their pharmacological activity was determined with the objective to better understand their structure–activity relationship (SAR) for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by maximal electroshock seizure (MES) test and subcutaneous pentylenetetrazole (scPTZ) test models in mice. All compounds substituted with cyclopropyl group at fifth position of hydantoin ring showed better protection against MES test. Compounds 5b, 5d, 5e, 5g and 5j were found to be the most potent compounds of this series and compared with the reference drug phenytoin sodium in MES test. Compound 5j also showed equipotent activity with the standard drug sodium valproate at the doses of 20 and 40 mg kg−1 in scPTZ test.A series of new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and evaluated for anticonvulsant activity. Their pharmacological activity was determined with the objective to better understand their structure–activity relationship (SAR).

Effect of N-trimethyl chitosan enhancing the dissolution properties of the lipophilic drug cyclosporin A

Co-reporter:Xiaoju Zhou, Yan Hu, Yanping Tian, Xianming Hu

Carbohydrate Polymers 2009 Volume 76(Issue 2) pp:285-290

Publication Date(Web):17 March 2009

DOI:10.1016/j.carbpol.2008.10.018

The aim was to evaluate the influence of N-trimethyl chitosan chloride (TMC) as a carrier for solid dispersion on the dissolution of poorly water-soluble drugs. In this study, we used cyclosporin A(CyA) as a model drug and TMC as a carrier. The effect of various formulation and process variables including TMC-to-CyA mixing weight ratio, weigh molecular(Mw) of TMC and methods used to disperse CyA along with the TMC on the drug dissolution was investigated. The nature of CyA dispersed in the matrix was studied by powder X-ray diffractometry (PXRD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and dissolution rate analyses. It was proved that all solid mixtures of CyA with TMCs showed a significantly rapid dissolution rate compared to pure drug and physical mixture. The greater the TMC content the higher the drug dissolution was, up to a maximum corresponding to a polymer: drug ratio of 3:1. The lower the Mw of TMC, the more important the polymer effect was. The dissolution of CyA was remarkably improved by the solid dispersion. The drug dissolution enhancement was attributed to the decreased drug crystallinity and size and polymer wetting effect. There was no significant difference in the efficiency of improving the drug dissolution between the solid dispersions prepared by solvent dispersing and by co-grinding. It was suggested that the TMC with a lower molecular weight is a useful carrier for solid dispersion.

Asymmetric reduction of acetophenone using α,α-disubstituted aziridinemethanols and borane

Co-reporter:Wenjin Xu, Hao Guo, Jun Zhang, Qifeng Zhu, Xianming Hu

Journal of Molecular Catalysis A: Chemical 2009 300(1–2) pp: 25-28

Publication Date(Web):

DOI:10.1016/j.molcata.2008.10.031

Potential tridentate salicylaldehyde hydrazone of arylalkanoic acid coordinate to copper(II) acting as dinegative tetradentate ligands

Co-reporter:Lamei Wu, Guofu Qiu, Hanbing Teng, Qifeng Zhu, Shucai Liang, Xianming Hu

Inorganica Chimica Acta 2007 Volume 360(Issue 9) pp:3069-3074

Publication Date(Web):10 June 2007

DOI:10.1016/j.ica.2007.03.001

A chiral Schiff base N-(S)-2-(6-methoxylnaphthyl)-propanoyl-N′-(2-hydroxylbenzylidene)hydrazine (H2L) has been synthesized. Reaction of H2L with Cu(OAc)2 · H2O led to the formation of a metal complex {[CuL] · H2O · 2DMF}∞ (1). In complex 1, the potential dinegative tridentate L2− ligand acting as tetradentate bridging ligand coordinate to two metal ions so as to form a novel infinite metal–organic coordination chain structure. The enantiomerically pure ligand H2L presents two different sets of signals in the 1H NMR spectrum either in chloroform solution or in dimethylsulfoxide solution, showing the presence of both (E) and (Z) isomers. The X-ray structural investigations of H2L revealed that it is the fully extended E-configuration in the solid state.Potential tridentate ligands N-(S)-2-(6-methoxylnaphthyl)-propanoyl-N′-(2-hydroxylbenzylidene) hydrazine acting as tetradentate bridging ligands coordinate to two metal ions to form a novel infinite metal–organic coordination chain structure.

Preparation, characterization and tableting properties of two new pachyman-based pharmaceutical aids: I. disintegrants in dispersible tablets

Co-reporter:Yuling Xiao;Shucai Liang;Guofu Qiu;Jianyuan Wu;Junbo Zhang

Polymers for Advanced Technologies 2007 Volume 18(Issue 4) pp:268-274

Publication Date(Web):12 MAR 2007

DOI:10.1002/pat.849

Linear pachyman was isolated from the sclerotium of Poria cocos. Its hydroxypropyl and carboxymethyl derivatives, with considerable hydrophilicities, were synthesized. Their chemical structures, biocompatibilities, powder and tableting properties were determined. To exploit their novel applications in tablet excipients, ampicillin and probenecid dispersible tablets were compressed using the two derivatives as disintegrants, respectively. The detailed characterization of the tablets indicated the great potential of the two synthesized derivatives to be used as pharmaceutical excipients. Copyright © 2007 John Wiley & Sons, Ltd.

Copper(II) Complexes of Salicylaldehyde Hydrazones: Synthesis, Structure, and DNA Interaction

Co-reporter:Han-Bing Teng;La-Mei Wu;Xian-Bing Ke;Wen-Jin Xu;Jiang-Tao Su;Xian-Ming Hu;Shu-Cai Liang

Chemistry & Biodiversity 2007 Volume 4(Issue 9) pp:2198-2209

Publication Date(Web):21 SEP 2007

DOI:10.1002/cbdv.200790177

Three hydrazone ligands, H₂L1–H₂L3, made from salicylaldehyde and ibuprofen- or naproxen-derived hydrazides, were prepared and transformed into the corresponding copper(II) complexes [Cu^IIL1]⋅H₂O, [Cu^IIL2], and [(Cu^II)₂(L3)₂]⋅H₂O⋅DMF (Scheme). The X-ray crystal structure of the last-mentioned complex was solved (Fig. 1), showing a square-planar complexation geometry, and the single units were found to form a one-dimensional chain structure (Fig. 2). The interactions of these complexes with CT-DNA were studied by different techniques, indicating that they all bind to DNA by classical and/or non-classical intercalation modes.

Aza-Payne rearrangement of α,α-disubstituted-aziridinemethanols

Co-reporter:Feng Xichun, Qiu Guofu, Liang Shucai, Teng Hanbing, Wu Lamei, Hu Xianming

Tetrahedron: Asymmetry 2006 Volume 17(Issue 9) pp:1394-1401

Publication Date(Web):15 May 2006

DOI:10.1016/j.tetasy.2006.04.035

The aza-Payne rearrangement of activated N-Ts-α,α-disubstituted-aziridinemethanols, induced by NaOH in the mixed solvent tBuOH/H2O/THF (4:5:1) or NaH in a mixed solvent of THF/HMPA (10:1), as well as some N-Boc-α,α-disubstituted-aziridinemethanols with the latter reagent/solvent combination, provides the corresponding epoxides in up to 99% yield.(2S,3S)-3-Methylaziridin-2-yl(diphenyl)methanolC16H17NO[α]D20=+80.0 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-3-Methylaziridin-2-yl(dibutyl)methanolC12H25NO[α]D20=-10.5 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-3-Methylaziridin-2-yl(dibenzyl)methanolC18H21NO[α]D20=-23.2 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-3-Methylaziridin-2-yl(bis(4-methoxyphenyl))methanolC18H21NO3[α]D20=+58.7 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S)-Aziridin-2-yl(diphenyl)methanolC15H15NO[α]D20=-22.6 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)(2S)-Aziridin-2-yl(dibutyl)methanolC11H23NO[α]D20=-21.4 (c 10.0, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)(2S)-Aziridin-2-yl(dibenzyl)methanolC17H19NO[α]D20=-28.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)(2S)-Aziridin-2-yl(bis(4-methoxyphenyl))methanolC17H19NO3[α]D20=+67.0 (c 9.0, THF)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)(2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)diphenylmethanolC23H23NO3S[α]D20=+22.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)dibutylmethanolC19H31NO3S[α]D20=-5.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)dibenzylmethanolC25H27NO3S[α]D20=-58.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)bis(4- methoxyphenyl)methanolC25H27NO5S[α]D20=+32.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(S)-(1-Tosylaziridin-2-yl)diphenylmethanolC22H21NO3S[α]D20=-35.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(S)-(1-Tosylaziridin-2-yl)dibutylmethanolC18H29NO3S[α]D20=-24.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(S)-(1-Tosylaziridin-2-yl)dibenzylmethanolC24H25NO3S[α]D20=-47.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2R,3S)-N-(1-(3,3-Diphenyloxiran-2-yl)ethyl)-4-methylbenzenesulfonamideC23H23NO3S[α]D20=+130.7 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S)(2R,3S)-N-(1-(3,3-Dibutyloxiran-2-yl)ethyl)-4-methylbenzenesulfonamideC19H31NO3S[α]D20=+36.2 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S)(2R,3S)-N-(1-(3,3-Dibenzyloxiran-2-yl)ethyl)-4-methylbenzenesulfonamideC25H27NO3S[α]D20=-28.9 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S)(2R,3S)-N-(1-(3,3-Bis(4-methoxyphenyl)oxiran-2-yl)ethyl)-4-methylbenzenesulfonamideC25H27NO5S[α]D20=-26.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3S)(2R)-N-((3,3-Diphenyloxiran-2-yl)methyl)-4-methylbenzenesulfonamideC22H21NO3S[α]D20=+84.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(2R)-N-((3,3-Dibutyloxiran-2-yl)methyl)-4-methylbenzenesulfonamideC18H29NO3S[α]D20=+37.4 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(2R)-N-((3,3-Dibenzyloxiran-2-yl)methyl)-4-methylbenzenesulfonamideC24H25NO3S[α]D20=+40.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(2S,3S)-tert-Butyl 2-(hydroxydiphenylmethyl)-3-methylaziridine-1-carboxylateC21H25NO3[α]D20=-1.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2S,3S)-tert-Butyl 2-(hydroxybis(4-methoxyphenyl)-3-methylaziridine-1-carboxylateC23H29NO5[α]D20=-9.8 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)(2R,3S)-tert-Butyl 1-(3,3-diphenyloxiran-2-yl)ethylcarbamateC21H25NO3[α]D20=+78.0 (c 1.0, CHCl3)Source of chirality: asymmetrical synthesisAbsolute configuration: (2R,3S)(2R,3S)-tert-Butyl 1-(3,3-bis(4-methoxyphenyl)oxiran-2-yl)ethylcarbamateC23H29NO5[α]D20=+20.0 (c 0.6, CHCl3)Source of chirality: asymmetrical synthesisAbsolute configuration: (2R,3S)

The synthesis of substituted indazoles via cyclization of various hydrazones in the presence of polyphosphoric acid (PPA)

Co-reporter:Qiu Guofu;Su Jiangtao;Xu Wenjin;Hu Xianming;Wu Lamei;Feng Xichun

Journal of Heterocyclic Chemistry 2004 Volume 41(Issue 4) pp:601-604

Publication Date(Web):11 MAR 2009

DOI:10.1002/jhet.5570410420

Research directed toward the discovery of nitric oxide synthase inhibitor led to synthesis of a series of substituted indazoles via the intramolecular cyclization of various hydrazones of substituted acetophenones and benzophenones in the presence of polyphosphoric acid (PPA). The structures of the indazoles were determined by elemental analysis, H nmr, ir, and ms.

Selective oxidation of spirolactone-related sulfides to corresponding sulfoxides and sulfones by hydrogen peroxide in the presence of N-hydroxysuccinimde

Co-reporter:Zhi-Gang Xiong, Jun Zhang, Xian-Ming Hu

Applied Catalysis A: General (1 January 2008) Volume 334(Issues 1–2) pp:44-50

Publication Date(Web):1 January 2008

DOI:10.1016/j.apcata.2007.09.029

Significant steroids: effective and general synthesis of 4α- and 4β-amino-5α-androstanes

Co-reporter:Xianbing Ke, Hao Hu, Keda Zhang, Wenjin Xu, Qifeng Zhu, Lamei Wu and Xianming Hu

Chemical Communications 2009(Issue 9) pp:NaN1039-1039

Publication Date(Web):2009/01/27

DOI:10.1039/B817910G