Prediction of novel drug targets in Ergosterol biosynthesis pathway: A proposed mechanism of anticandidal activity of green tea phytocompounds

Jigisha Anand, Prabhakar Semwa

Abstract

The emergence of antibiotic resistance in pathogenic Candida species has led to explore new alternative therapies to combat its associated life threatening infections. Synergistic anticandidal potentials of green tea (derived from Camellia sinensis) with antifungal agents is well known. Our study aims at predicting the novel inhibitory targets of green tea (GT) phytocompounds and pretending the inhibitory mechanism involved in synergistic inhibition of GT with antifungals. The interaction of GT phytocompounds and ergosterol synthesising proteins (ERG) of the Candida species has been assessed by in silico study using iGEMDOCK software which revealed ERG 26, ERG 6, ERG 25, and ERG 8 proteins as novel drug targets of kaempferitrin, EGCG, ECG, chlorogenic acid respectively present in GT.Supporting our investigation, in vitro studies have been done with GT leaves from different geographical locations. Catechins were purified and identified by HPLC and synergistic effect of solvent extracts and purified catechins with fluconazole (Flu), Amphotericin B (AmB) against Candida albicans and Candida glabrata depicted the convincing synergistic inhibitory effect of GT. The simultaneous interaction of GT and antifungals with ERG proteins could be the prohibitory mechanism that inhibits the growth of Candida species implying the candidacidal synergy between GT and antifungals.

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