Design,Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains |
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| Authors: | Tingjunhong Ni Zichao Ding Fei Xie Yumeng Hao Junhe Bao Jingxiang Zhang Shichong Yu Yuanying Jiang Dazhi Zhang |
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| Affiliation: | 1.Department of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China;2.Department of Organic Chemistry, School of Pharmacy, Navy Medical University, No. 325 Guohe Road, Shanghai 200433, China; (Z.D.); (F.X.); (Y.H.); (J.B.);3.Center for New Drug Research, School of Pharmacy, Navy Medical University, No. 325 Guohe Road, Shanghai 200433, China; |
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| Abstract: | A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation. |
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| Keywords: | triazole CYP51 antifungal molecular docking synthesis |
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