Relative Eccentric Distance Sum/Product Indices for QSAR/QSPR: Development, Evaluation, and Application

Abstract

In the present study, five detour/distance matrix based molecular descriptors (MDs) termed as relative eccentric distance sum/product indices (denoted by Rξ1SV, Rξ2SV, Rξ3SV, RPξ1SV, and RPξ2SV), as well as their topochemical versions denoted by (Rξ1cSV, Rξ2cSV, Rξ3cSV, RPξ1cSV, and RPξ2cSV) have been conceptualized for exclusive use for molecules containing cyclic moieties. The said MDs exhibited exceptionally high discriminating power and high sensitivity toward branching/relative position of substituents in cyclic structures amalgamated with negligible degeneracy. Subsequently, the proposed MDs along with other MDs were successfully utilized for the development of models for the prediction of human glutaminyl cyclase (hQC) inhibitory activity using decision tree (DT), random forest (RF) and moving average analysis (MAA). A data set comprising of 45 analogues of substituted 3-(1H-imidazol-1-yl) propyl thiourea derivatives was used. DT identified proposed relative eccentric distance sum topochemical index-1 as the most important MD. High accuracy of prediction up to 96%, 93%, and 95% was observed in case of models derived from decision tree, random forest, and MAA, respectively. The statistical significance of proposed models was assessed through specificity, sensitivity, overall accuracy, Mathew’s correlation coefficient (MCC), and intercorrelation analysis.