Abstract

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP STUDY ON THE MMP-13 INHIBITORY ACTIVITY OF FUSED PYRIMIDINE DERIVATIVES POSSESSING A NON-CARBOXYLATE ZINCBINDING FUNCTION

Jahan Afsar, Meena Dinesh Kumar and Sharma Brij Kishore*

Abstract

QSAR study has been carried out on the MMP-13 inhibitory activity of fused pyrimidine derivatives possessing a non-carboxylate zincbinding function in 0D- to 2D-Dragon descriptors. The derived QSAR models have revealed that the information content indices of 1st and 2nd order neighborhood symmetry (descriptors IC1 and IC2), Lovasz- Pelikan index (descriptor LP1), maximal electrotopological positive variation (descriptor MAXDP) and molecular walk count of order 09 (descriptor MWC09) played a pivotal role in rationalization of MMP- 13 inhibition activity of titled compounds. Atomic properties such as mass and atomic Sanderson electronegativity in terms of atomic properties weighted descriptors MATS2m, GATS3e, GATS4e, GATS7e and Me, certain atom centred fragments such as R-C(=X)-X/R-C#X/X-=C=X (descriptor C-040) and aliphatic hydroxylamine functionality (descriptor nNHOH) are also predominant to explain MMP-13 inhibition actions of fused pyrimidines. PLS analysis has also corroborated the dominance of CP-MLR identified descriptors. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.

Keywords: QSAR; MMP-13 inhibitory activity; Combinatorial protocol in multiple linear regression (CP-MLR) analysis; PLS analysis; Dragon descriptors; Fused pyrimidines. Non-carboxylate zinc binding group.