A Quantitative Structure-Activity Relationship Study of Caffeic Acid Amides as Selective Inhibitors of Matrix Metalloproteinase
Prithvi Pal Singh · 2013
A quantitative structure-activity relationship (QSA R) study is carried out on caffeic acid amides as t he inhibitors of matrix metalloproteinase (MMP). The i nhibition action, for the sub-type MMP-9, is quanti tatively 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 t o 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 electro negativities (MATS6e). Additionally, the Balaban-type index obtained from polarizabi lity weighted distance matrix (Jhetp) and Randic shape i ndex representing the ratio of path over walk count of order 4 (PW4) also showed prevalence in the rationalizati on of activity profiles. The partial least squares (PLS) analysis further confirmed the dominance of the CP ‐MLR identified descriptors. The guidelines delineat ed by the Fujita-Ban approach, statistically validated mo dels and PLS analysis, facilitated in exploring som e potential analogues of the series. Applicability domain (AD) analysis revealed that the suggested models have ac ceptable predictability.