Predicting anti-HIV activity of TIBO derivatives: a computational approach using a novel topological descriptor.

A novel highly discriminating adjacency-cum-distance-based topological descriptor, termed the adjacent eccentric distance sum index, has been conceptualized and its discriminating power investigated with regard to the anti-HIV activity of 4,5,6,7-tetrahydro-imidazo-[4,5,1- jk] [1,4] benzodiazepin-2 (1 H)-one (TIBO) derivatives. The discriminating power of the adjacent eccentric distance sum index was compared with that of the eccentric connectivity index - another adjacency-cum-distance-based topological descriptor. The values of the eccentric connectivity index and the adjacent eccentric distance sum index of each of 121 analogues comprising the data set were computed and active ranges were identified. Subsequently, a biological activity was assigned to each analogue involved in the data set and this was then compared with the reported anti-HIV activity. Excellent correlations were observed between anti-HIV activity and both the topological descriptors. Although the overall accuracy of prediction was found to be approximately 84% in case of the eccentric connectivity index and approximately 86% in case of adjacent eccentric distance sum index, the predictability using the adjacent eccentric distance sum index in the active range itself was >92%. The proposed index offers a vast potential for structure-activity/property studies.