Synthesis, structure-activity relationship and evaluation of antifungal activity of tryptanthrin derivatives against drug-resistant Candida albicans

With the increasing of Candida albicans infections year by year, and the widespread use of azole drugs, especially fluconazole has led to the emergence of drug resistance. Therefore, new antifungal agents are urgent needed. In this work, we synthesized a series of tryptanthrin derivatives, and all compounds were evaluated for antifungal activities against Candida albicans in vitro. The results indicated that most compounds combined with fluconazole showed good antifungal activity against drug-resistant Candida albicans. Especially, compound 5b combined with fluconazole had an excellent synergistic effect, with MIC₅₀ value of 0.94 μg/mL, and the FICI value of 0.005. Further mechanism study demonstrated that compound 5b significantly inhibited the hyphal growth and biofilm formation of Candida albicans. Compound 5b combined with fluconazole could be considered as a novel antifungal agent.