Chebulinic Acid for Alternative Treatment of Vulvovaginal Candidiasis by Targeting Agglutinin-Like Sequence Protein 3 in Candida albicans: In silico Approach

Abstract

Chebulinic acid, a chemotaxonamic marker of Terminalia chebula has been described in Ayurveda, Unani and homeopathy traditional medicinal system for the treatment of various fungal diseases. Almost 70-80 % of women are currently affected from vulvovaginal candidiasis and the overgrowth of Candida albicans is the major reason behind it. The aim of the present study was to determine the efficacy of chebulinic acid in inhibiting adhesion as well as growth of Candida albicans inside the host in comparison with currently available azole derivatives in the market. The inhibitory effect of chebulinic acid was determined by spectrophotometric growth curve analysis reflecting 10 % lower minimum inhibitory concentration value of fluconazole, ketaconazole, itraconazole and chebulinic acid. Virtual docking study was carried out at catalytic domain of agglutinin-like sequence protein 3 chain A and B respectively, to determine the binding affinity and its active binding sites. Chebulinic acid exhibited high sensitivity against Candida albicans with minimum inhibitory concentration of (0.025 μg/ml) followed by ketaconazole (0.05), itraconazole (0.048) and fluconazole (1.5). An extended lag phase and a decline in overall growth were observed in Candida albicans when compared to control when grown in presence of chebulinic acid. At ASN22, TYR23, TRP224, ASP169, TYR166, ASP162, ASN225 GLY297, ARG294 and ASP162, ASN160, ASP169, THR168, TYR166, TYR226, chebulinic acid binds with agglutinin-like sequence protein 3 chain A and B respectively with binding affinity of -10.4 and -9.8 kcal/mol. Our present study strengthens the evidences which stand in support of the fact that chebulinic acid can be used as potent inhibitor of Candida albicans than other commercially available synthetic anti-fungal drugs.