Novel antifungal compound from Prunella vulgaris: An in-silico approach towards the discovery of potent inhibitor to combat phytopathogenic fungi

Abstract

Phytopathogenic fungi wreak havoc on crops, causing substantial losses globally. Numerous chemical fungicides are employed to manage the pathogen, yet effectiveness is limited and resistance concerns are rising. The current study aimed to identify the antifungal compound from the spikes of a significant medicinal herb Prunella vulgaris subsp. hispida (Benth.) Hultén as an alternative to combat the fungi. In vitro, antifungal assay revealed that the ethyl acetate extract of P. vulgaris emerged as a potent inhibitor against selected fungal phytopathogens Fusarium oxysporum, Alternaria solani and Penicillium digitatum. Through chromatographic analysis, 32 compounds were identified from the active fraction of ethyl acetate extract. Notably, five compounds were reported for the first time from P. vulgaris. They include dichloroacetic acid, tridec-2-ynyl ester (1), phenol, 3,5-bis(1,1-dimethylethyl)- (2), 2-thiopheneacetic acid, 3-tetradecyl ester (3), 1H-1,2,4-triazol-3-amine, 1-ethyl- (4) and sulfurous acid, octadecyl 2-propyl ester (5). Compound 1 was identified as the most abundant. NMR studies confirmed the presence of compound 1, prompting its selection for in silico antifungal analysis. Various computational models showcased that Compound 1 achieved a high bioactive score and met the criteria for medicinal chemistry friendliness. Additionally, a molecular docking study revealed that compound 1 displayed a good binding affinity with the multiple target fungal enzymes such as scytalone dehydratase and cytochrome P450 which is a prime target for antifungal drugs. Remarkably, this study marks the first detection of compound 1’s effectiveness against phytopathogenic fungi. Therefore, compound 1 holds the potential to pave the way for the development of a potent novel fungicide.