Hologram Based QSAR Analysis of Caspase-3 Inhibitors

Abstract

Caspases, a family of cysteinyl aspartate–specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage because the activation of caspases-3 stimulates a signalling pathway that ultimately leads to the death of the cell. In this study, Hologram based Quantitative Structure Activity Relationship (HQSAR) models was generated on a series of Caspase-3 inhibitors named 3, 4-dihydropyrimidoindolones derivatives. The best HQSAR model was obtained using atoms, bonds, and hydrogen atoms (A/B/H) as fragment distinction parameter using hologram length 61 and 3 components with fragment size of minimum 5 and maximum 8. Significant cross-validated correlation coefficient (q2= 0.684) and non cross-validated correlation coefficients (r2= 0.754) were obtained. The model was then used to evaluate the eight external test compounds and its r2 pred was found to be 0.559. Contribution map show that presence of pyrrolidine sulfonamide ring and its bulkier substituent’s makes big contributions for improving the biological activities of the compounds.