Twenty-nine novel triazole analogues of ravuconazole and isavuconazole were designed and synthesized. Most of the compounds exhibited potent in vitro antifungal activities against 8 fungal isolates. Especially, compounds a10, a13, and a14 exhibited superior or comparable antifungal activity to ravuconazole against all the tested fungi. Structure-activity relationship study indicated that replacing 4-cyanophenylthioazole moiety of ravuconazole with fluorophenylisoxazole resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum.Twenty-nine novel triazole analogues of ravuconazole and isavuconazole were designed and synthesized. Structure-activity relationship study indicated that replacing 4-cyanophenylthioazole of ravuconazole with fluorophenylisoxazole resulted in antifungal triazoles with more effectiveness and a broader-spectrum.Download high-res image (134KB)Download full-size image

Based on our previous discovery and SAR study on the lead compounds 7d, 5 and berberine which can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, a series of 3-(benzo[d][1,3]dioxol-5-yl)-N-(substituted benzyl)propanamides were designed, synthesized, and evaluated for their in vitro synergistic activity in combination with fluconazole. The series 2a–f were designed by replacing the amide moiety of the lead compound 7d with retro-amide moiety, and compounds 2a and 2b showed more activity than the lead 7d. Furthermore, introducing biphenyl moiety into series 2d–f afforded series 3a–r, most of which exhibited significantly superior activity to the series 2d–f. Especially, compound 3e, at a concentration of 1.0 µg/ml, can enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans from 128.0 µg/ml to 0.125–0.25 µg/ml. A clear SAR of the compounds is discussed.A series of 3-(benzo[d][1,3]dioxol-5-yl)-N-(substituted benzyl)propanamides were designed, synthesized, and evaluated for their in vitro synergistic activity enhancing the susceptibility of fluconazole against fluconazole-resistant Candida albicans. Compound 3e, at a concentration of 1.0 µg/ml, can enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans from 128.0 µg/ml to 0.125–0.25 µg/ml. A clear SAR of the compounds is discussed.Download high-res image (198KB)Download full-size image

A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3–30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 μg/ml, decreased the MIC80 of fluconazole from 128.0 μg/ml to 1.0–0.5 μg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.A series of caffeic acid amides 3–13 were designed and synthesized through scaffold hopping from berbeine and 2, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3–30 except 26 exhibited potent activity. The SAR study indicates that the dihydroxyl groups and the amido group in the caffeic acid amides are the important pharmacophores.

A concise, highly convergent synthesis of camptothecin in good yield from readily accessible building blocks is reported. The key step in this approach is to construct the C ring of camptothecin by coupling two blocks via the Suzuki reaction, followed by a mild one-step, one-pot cyclization, wherein the methoxypyridine nitrogen in the D/E ring block displaces the activated hydroxyl group in the ring A/B block while the methoxy group is cleaved in situ. The key intermediate 12 was obtained in 73% overall yield in three steps.

To develop a selective and sensitive fluorescent turn-on chemodosimeter for copper ions in neutral buffered media, a novel rhodamine hydrazone derivative bearing a piperidinyl group was synthesized. Upon addition of Cu2+, the ring-opening process of rhodamine spirolactam was found to result in remarkably enhanced fluorescent and colorimetric labeling, whereas very little fluorescence variations or color changes were observed in the presence of other metal ions (K+, Na+, Ca2+, Mg2+, Mn2+, Ag+, Sn2+, Hg2+, Pb2+, Fe2+, Fe3+, Zn2+, Co2+, and Ba2+). The detection limit of this newly developed probe was shown to be up to 76 ppb. Importantly, the probe was successfully used for fluorescence imaging in Caco-2 cells.