Department of Chemistry, S.K. Government Post-Graduate College, Sikar-332 001, India
E-mail: [email protected]
A quantitative structure-activity relationship (QSAR) study is carried out on caffeic acid amides as the inhibitors of matrix metalloproteinase (MMP). The inhibition action, for the sub-type MMP-9, is quantitatively analyzed following the non-parametric (Fujita-Ban) and parametric approaches. The Fujita-Ban analysis has identified the substituents which imparted highest contributions to parent moiety, makes it feasible to design more active analogues of the series. The parametric approach, on the other hand, utilized molecular 2D-descriptors to develop statistical validated models through combinatorial protocol in multiple linear regression analysis (CP-MLR). The descriptors, participated in the most significant models, have highlighted the role of Moran autocorrelations of lag-4 and lag-6 weighted, respectively, by atomic masses (MATS4m) and atomic Sanderson electronegativities (MATS6e). Additionally, the Balaban-type index obtained from polarizability weighted distance matrix (Jhetp) and Randic shape index representing the ratio of path over walk count of order 4 (PW4) also showed prevalence in the rationalization of activity profiles. The partial least squares (PLS) analysis further confirmed the dominance of the CP‐MLR identified descriptors. The guidelines delineated by the Fujita-Ban approach, statistically validated models and PLS analysis, facilitated in exploring some potential analogues of the series. Applicability domain (AD) analysis revealed that the suggested models have acceptable predictability.
Key words: Caffeic acid amide derivatives, MMP-9 inhibitors, combinatorial protocol in multiple linear regression (CP-MLR) analysis, QSAR study, DRAGON 2D-descriptors.