Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China.
Department of Organic Chemistry, School of Pharmacy, Navy Medical University, No. 325 Guohe Road, Shanghai 200433, China.
Molecules. 2022 May 24;27(11):3370. doi: 10.3390/molecules27113370.
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 and showed excellent in vitro activities against (MIC = 0.125, 0.0625 μg/mL), (MIC = 0.125, 0.0625 μg/mL), and (MIC = 8.0, 4.0 μg/mL). Compound also exerted superior activity to compound and fluconazole in inhibiting hyphae growth of and inhibiting drug-resistant strains of , and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that could effectively protect mice models from infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound deserves further investigation.
设计、合成了一系列含苯乙炔基吡唑侧链的三唑衍生物，其中大多数表现出良好的体外抗真菌活性。特别是化合物 和 对 （MIC=0.125、0.0625μg/mL）、 （MIC=0.125、0.0625μg/mL）和 （MIC=8.0、4.0μg/mL）表现出优异的体外活性。化合物 对 和 的抑菌活性优于化合物 和氟康唑，在 1.0mg/kg 剂量下能降低小鼠肾脏中的真菌负荷。体内药效评价表明，化合物 在 0.5、1.0 和 2.0mg/kg 剂量下能有效保护小鼠免受 感染。这些结果表明，化合物 值得进一步研究。
