Fifty-two kinds of N′-phenylhydrazides were successfully designed and synthesized. Their antifungal activity in vitro against five strains of C. albicans (Candida albicans) was evaluated. All prepared compounds showed varying degrees of antifungal activity against C. albicans and their MIC₈₀ (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 C. albicans 4395 and 5272 were much better than those of fluconazole. The MIC₈₀ values of 14/52 compounds against fluconazole-resistant fungus C. albicans 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSI_B = 12.0). A₁₁ showed the best inhibitory activity against C. albicans SC5314, 4395, and 5272 (MIC₈₀ = 1.9, 4.0, and 3.7 μg/mL). The antifungal activities of B₁₄ and D₅ against four strains of fluconazole-resistant fungi were better than those of fluconazole. The TAI values of A₁₁ (2.71), B₁₄ (2.13), and D₅ (2.25) are the highest. Further exploration of antifungal mechanisms revealed that the fungus treated with compound A₁₁ produced free radicals and reactive oxygen species, and their mycelium morphology was damaged. In conclusion, the N′-phenylhydrazide scaffold showed potential in the development of antifungal lead compounds. Among them, A₁₁, B₁₄, and D₅ demonstrated particularly promising antifungal activity and held potential as novel antifungal agents.

Fifty-two kinds of N’-phenylhydrazides were successfully designed and synthesized. Their anti-fungal activity in vitro against five strains of C. alb. was evaluated. All prepared compounds owned varying degrees of activity and their MIC80, TAI, and TSI values were calculated. The in-hibitory activities of 27/52 compounds against fluconazole-resistant fungi C. alb. 4395 and C. alb. 5272 were much higher than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. alb. 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the highest inhibitory activity against C. alb. SC5314, 4395, and 5272. The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were higher than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploring the antifungal mechanism revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium mor-phology was damaged. In conclusion, the hydrazide scaffold showed potential in the develop-ment of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and hold potential as novel antifungal agents.