In silico analysis and in vitro inhibition studies of glutathione s transferases

Abstract

Glutathione S-transferases are drug targets. Though several isoforms of GSTs are present, increased expression GSTP is associated with both malignancy and drug resistance. The concept of structural similarity of the drug target GST with its isoforms causes the need for the development of specific drugs. The helminth GSTs are able to conjugate glutathione to xenobiotic compounds or to bind to the anthelminth drugs. GST is usually found to be localized near to host-parasite interface. This enzyme has been identified as a potentially vulnerable target in immunotherapy and chemotherapy of parasitic diseases newlineAs a result of screening of natural products, plant polyphenols have been identified as a group of plant metabolites that are known to interact with human GST enzymes. In silico screening of natural products has been performed to identify the specific inhibitors of Human GSTP and Wuchereria bancrofti GST. The phytochemicals which are specific to the H site of human GSTP and WbGST were identified. newlineThe phylogenetic analysis of Human GSTs revealed that the human GSTP is phylogenetically more related to GSTA than the other GSTs. The phylogenetic analysis of helminth parasitic GST revealed that the Wuchereria bancrofti, Brugia malayi and Oncocerca species are closely related. The organ specific expression of GSTs has been analyzed for the statistical significance of variation in gene expression and the results of two-way analysis of variance (ANOVA) shows that the variations in the level of expression of GST isozymes are statistically significant newline