Synthesis and activity of 1,2,3-Triazolyl-chalcones against the Fungus Colletotrichum lindemuthianum

Abstract

Background: Anthracnose, caused by the fungus Colletotrichum lindemuthianum, is one of the most important diseases that affect common beans. As some chalcones and triazoles are active cores against fungi, 1,2,3-triazolyl-chalcone hybrids could present more intense antifungal activities than the fungicides commercially available.

Objective: The present work aimed at synthesizing these hybrids, evaluating them as antifungal agents against C. lindemuthianum, and identifying the enzymatic target of the most active substances using in silico calculations.

Method: 1,2,3-triazole aldehydes and acetophenones underwent Claisen-Schmidt reactions to afford four known and six new hybrids, which were identified by spectrometric techniques. In vitro antifungal activities of these compounds against C. lindemuthianum were determined by MIC method. The most active compounds also underwent an assay with common bean plants inoculated with this fungus. An in silico study comprising pharmacophoric search and molecular docking was carried out with the most active substances.

Results: Most of the compounds exhibited good to reasonable in vitro activity, and four of them displayed higher activity than the commercial fungicide methyl thiophanate. Among six 1,2,3-triazolylchalcones with the lowest MIC values, three of them reduced the anthracnose severity in common beans plants to levels similar to those observed for plants treated with methyl thiophanate. According to the in silico studies, these substances act against C. lindemuthianum through inhibition of the serine/ threonine-protein kinase and fatty acid synthase.

Conclusion: 1,2,3-triazolyl-chalcone hybrids are very active against C. lindemuthianum. Apparently, they are able to inhibit two different enzymes produced by the fungus.