College of Chemistry & Pharmacy, Northwest A & F University, Yangling 712100, China.
Key Laboratory of Botanical Pesticide R & D in Shaanxi Province, Northwest A & F University, Yangling 712100, China.
Int J Mol Sci. 2023 Oct 12;24(20):15120. doi: 10.3390/ijms242015120.
Fifty-two kinds of '-phenylhydrazides were successfully designed and synthesized. Their antifungal activity in vitro against five strains of () was evaluated. All prepared compounds showed varying degrees of antifungal activity against and their MIC (the concentration of tested compounds when their inhibition rate was at 80%), TAI (total activity index), and TSI (total susceptibility index) were calculated. The inhibitory activities of 27/52 compounds against fluconazole-resistant fungi 4395 and 5272 were much better than those of fluconazole. The MIC values of 14/52 compounds against fluconazole-resistant fungus 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSI = 12.0). showed the best inhibitory activity against SC5314, 4395, and 5272 (MIC = 1.9, 4.0, and 3.7 μg/mL). The antifungal activities of and against four strains of fluconazole-resistant fungi were better than those of fluconazole. The TAI values of (2.71), (2.13), and (2.25) are the highest. Further exploration of antifungal mechanisms revealed that the fungus treated with compound produced free radicals and reactive oxygen species, and their mycelium morphology was damaged. In conclusion, the '-phenylhydrazide scaffold showed potential in the development of antifungal lead compounds. Among them, , , and demonstrated particularly promising antifungal activity and held potential as novel antifungal agents.
成功设计和合成了 52 种 -苯腙。评估了它们对五种（）菌株的体外抗真菌活性。所有制备的化合物对和它们的 MIC（当抑制率为 80%时测试化合物的浓度）、TAI（总活性指数）和 TSI（总敏感性指数）都表现出不同程度的抗真菌活性。27/52 种化合物对氟康唑耐药真菌 4395 和 5272 的抑制活性明显优于氟康唑。14/52 种化合物对氟康唑耐药真菌 5122 的 MIC 值小于 4μg/mL，因此它是最敏感的真菌（TSI = 12.0）。对 SC5314、4395 和 5272 的抑制活性最好（MIC = 1.9、4.0 和 3.7μg/mL）。和对四种氟康唑耐药真菌的抗真菌活性均优于氟康唑。（2.71）、（2.13）和（2.25）的 TAI 值最高。进一步探索抗真菌机制表明，用化合物处理的真菌产生自由基和活性氧，其菌丝形态受损。总之，-苯腙支架在开发抗真菌先导化合物方面具有潜力。其中，、、和表现出特别有希望的抗真菌活性，有潜力成为新型抗真菌药物。
