Abstract

CP-MLR/PLS DERIVED QSAR RATIONALES FOR THE MMP-13 INHIBITORY ACTIVITY OF THE INDOLE DERIVATIVES

Jahan Afsar, Sharma Brij Kishore* and Sharma Vishnu Dutt

Abstract

QSAR study has been carried out on the MMP-13 inhibitory activity of indole derivatives in 0D- to 2D-Dragon descriptors. The derived QSAR models have revealed that the information content index of 2nd order neighborhood symmetry (descriptor IC2) and average valence connectivity index chi-2 (descriptor X2A) in addition to molecular weight (descriptor MW), number of rotatable bonds (descriptor RBN), number of Oxygen atoms (descriptor nO) and aromatic ester functionality (descriptor nCOORPh) played a pivotal role in rationalization of MMP-13 inhibition activity of titled compounds. Atomic mass and polarizability weighted descriptors (MATS5m, BELm4 and GATS1p) and certain structural fragments such as H attached to C0(sp3) with 1X attached to next C (descriptor H-052) and CH3R/CH4 (descriptor C-001) are also predominant to explain MMP-13 inhibition actions of indole derivatives. 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; Indole derivatives.