Prediction of Carbonic Anhydrase activation by tri-/tetrasubstituted-pyridinium-azole compounds: A computational approach using novel topochemical descriptor

A novel highly discriminating adjacency-cum-distance based topochemical descriptor, termed as Superadjacency topochemical index, has been derived and its discriminating power investigated with regard to activation of Carbonic anhydrase (CA) isozyme-I by tri-/tetrasubstituted-pyridinium-azole compounds. The new index is not only sensitive to the presence of heteroatoms but also overcomes the problem of degeneracy of many topological descriptors. The discriminating power of Superadjacency topochemical index was found to be far superior when compared with that of distance based Wiener's index and adjacency based Molecular connectivity index. The values of Wiener's index, path-one Molecular connectivity index and Superadjacency topochemical index of each of the 42 substituted-pyridinium-azole compounds comprising the dataset were computed. Resultant data was analyzed and suitable models developed after identification of the active ranges. Subsequently, a biological activity was assigned to each of the compounds involved in the dataset using these models, which was then compared with the reported activation constants for Carbonic Anhydrase isozyme-I. Excellent correlations were observed between the activation constants of CA isozyme-I and all the topological/ topochemical descriptors. The overall accuracy of prediction was about 91% for models based upon both Molecular connectivity index as well as Wiener's index, and 96% for model based upon Superadjacency topochemical index. Surprisingly, the accuracy of prediction in the active range was found to be 100% in all the models. Thus the proposed index offers a vast potential for structure-activity/structure-property studies.