Topochemical models for predicting the activity of α,γ-diketo acids as inhibitors of the hepatitis c virus NS5B RNA-dependent RNA polymerase

Abstract

A relationship between the topochemical indices of α,γ-diketo acids and their inhibitory activity with respect to the hepatitis C virus NS5b RNA-dependent RNA polymerase has been studied. The values of Wiener’s topochemical index W c (a distance based descriptor), the Zagreb topochemical index M 2 c (an adjacency based descriptor), and the topochemical eccentric connectivity index ξ c c (an adjacency-cum-distance based descriptor) were calculated for a set of 30 compounds using an in-house computer program. The resulting data array was analyzed and the models of activity were developed after determination of the active ranges of parameters. Subsequently, a biological activity was assigned using these models to each compound included in the data bank, and the assignment was compared with data reported on the inhibitory activity. A high accuracy of prediction was observed for the proposed models. These models possess vast potential in providing basis structures for the development of diketo acids capable of effectively inhibiting the hepatitis C virus NS5b RNA-dependent RNA polymerase.