Quinic Acid Derivatives as Inhibitors of Glucosyltransferase Si, A Virulence Factor of Streptococcus Mutans in The Pathogenesis of Dental Caries

Abstract

The important prerequisite for the formation of dental caries is the ability of Streptococcus mutans to form the biofilm. It has been proved that the formation of biofilm is mediated mainly by the enzymatic action of the Glucosyltransferase (GTF) enzymes. These enzymes are considered fundamental for the virulence of S. mutans in the causation of dental caries. In the present study quinic acid derivatives have been developed insilico as the inhibitors of GTF-SI enzyme and a molecular docking study is preformed to find its efficiency as inhibitors. The three-dimensional structure of GTF-SI was retrieved from MMDB database. The possible binding sites of GTF-SI were searched using binding site prediction 3DLIGANDSITE. The structure of quinic acid was obtained from ZINC database. A total of 100 ligands were generated with the help of software ACD chemsketch. Rapid virtual screenings of these compounds were performed in the docking tool iGEMDOCK v2.0. Based on the binding energy a total of five ligands were selected for the further study. The selected five ligands were then analyzed for drug- relevant properties based on “Lipinski’s rule of five” and other drug like properties. The docking of five ligands was performed using AutoDock 4.0 software. From the present study, it has been found that (1R)-1,3,4-trihydroxy-5-methylcyclohexane carboxylic acid, which is a novel compound, a derivative of quinic acid, can act has an inhibitor for the GTF-SI