Antifungal activities of fluoroindoles against the postharvest pathogen Botrytis cinerea: In vitro and in silico approaches.

ABSTRACT

Botrytis cinerea is a common necrotrophic fungal pathogen, leading cause of gray mold diseases in plants and fruit. Several benzimidazoles are used for controlling B. cinerea-associated infection in fruit and vegetables, but benzimidazoles resistance restricts its further uses. Therefore, it is a need for alternative drugs that control B. cinerea. Indoles are multi-faceted compounds and their structural similarities with antifungal benzimidazoles make them a choice for further investigation. Thus, the main objective of the study was to investigate the antifungal potencies of indoles against B. cinerea and to decipher the molecular mechanism involved. We conducted in vitro antifungal assays, fruit assays, and computational studies of interactions between indoles and fungal microtubule polymerase. Of the 16 halogenated indoles examined, 4-fluoroindole, 5-fluoroindole, and 7-fluoroindole (MIC range 2-5 mg/L) were found to be more potent than the fungicides fluconazole and natamycin. Fluoroindoles inhibited or eradicated B. cinerea infections in tangerines and strawberries. Molecular dynamic simulation and density functional theory showed that these fluoroindoles stably interacted with microtubule polymerase. Quantitative structure-activity relationship analyses of halogenated indoles revealed that the presence of a fluoro group in the indole moiety is essential for anti-Botrytis activity. The plausibility of the underlying antifungal mechanism was confirmed by in vitro tubulin polymerization. Collective outcomes of this study indicates that fluoroindoles could be used as alternative fungicidal agents against B. cinerea.