Department of Organic Chemistry, School of Pharmacy, Naval Medical University, Shanghai, China.
Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2244696. doi: 10.1080/14756366.2023.2244696.
A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. antifungal activity studies demonstrated that most of the compounds inhibited the growth of six human pathogenic fungi. In particular, parts of phenyl-propionamide-containing compounds had excellent, broad-spectrum antifungal activity against SC5314, 22-21, 537 and 22-20 with MIC values in the range of ≤0.125 µg/mL-4.0 µg/mL. In addition, compounds , , , and showed inhibitory activities against fluconazole-resistant and . Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that , , and interfered with the ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of and with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.
设计并合成了一系列含有芳基-丙酰胺侧链的新型三唑衍生物。抗真菌活性研究表明，大多数化合物抑制了六种人体致病真菌的生长。特别是，含有苯丙酰胺的部分化合物对 SC5314、22-21、537 和 22-20 具有出色的广谱抗真菌活性，MIC 值在≤0.125 μg/mL-4.0 μg/mL 范围内。此外，化合物 、 、 、 和 对氟康唑耐药的 和 也表现出抑制活性。初步的构效关系（SAR）也进行了总结。此外，GC-MS 分析表明， 、 和 通过抑制 Cyp51 干扰麦角固醇生物合成途径。分子对接研究阐明了 与 Cyp51 的结合模式。这些化合物具有低溶血活性和有利的 ADME/T 特性，有望开发新型抗真菌药物。
