In silico molecular modelling studies and antibiofilm efficacy of shikonin against Candida albicans: mechanistic insight

Abstract

In the recent past, the occurrence of fungal infections has increased drastically and candidiasis, caused prominently by Candida albicans, is foremost among them which has caused significant mortality and morbidity majorly in immune-compromised patients. Shikonin is a well-known natural naphthazarin derivative with promising antifungal efficacy, but it's mechanism of action is still unclear. Keeping this in view, present workwas designed to get a mechanistic insight of anti-candida efficacy of shikonin via in vitro experiments and in situ molecular modelling studies. The current exploratory study is based on research that uses both qualitative and quantitative techniques, including minimum inhibitory concentration, minimum biofilm inhibitory concentration, time kill assay, cell cycle analysis and apoptotic assays, static biofilm formation assays, microscopic biofilm assessment assays, ergosterol content estimation and molecular docking/simulation studies. The study revealed a notable effect of shikonin against Candida albicans, including retardation of biofilms. Shikonin, with its increasing concentration leads to candidal cell apoptosis and necrosis establishing its dose-dependent effect. Additionally, it exhibited fungicidal activity via a mechanism of action likely related to ergosterol complexation which was further corroborated by molecular docking and simulation studies.