Chemometric Descriptor Based QSAR Rationales for the MMP-13 Inhibition Activity of Non-Zinc-Chelating Compounds
Brij Kishore Sharma · Medicinal Chemistry · 2013
The MMP-13 inhibition activity of non-zinc-chelating compounds has been quantitatively analyzed in terms of chemometric descriptors.The statistically validated quantitative structure-activity relationship (QSAR) models provided rationales to explain the inhibition activity of these compounds.The descriptors, identified through combinatorial protocol in multiple linear regression (CP-MLR) analysis, have highlighted the role of 3-path Kier alpha-modified shape index (S3K), complementary information content index of 1-order neighborhood symmetry (CIC1), eigenvalue sum from mass weighted distance matrix (SEigm), lowest eigenvalue n. 6 of Burden matrix / weighted by atomic van der Waals volumes (BELv6) and by atomic polarizabilities (BELp6), 3-order topological charge index (GGI3) and the functionality, R--CR--R (C-025).From statistically validated models, it appeared that the descriptors S3K, BELv6, BELp6 and SEigm make positive contribution to activity and their higher values are conducive in improving the MMP-13 inhibition activity of a compound.On the other hand, the descriptors CIC1, GGI3 and C-025 render detrimental effects to activity.Therefore, the absence of functionality, R--CR--R and lower values of descriptors CIC1 and GGI3 would be advantageous.PLS analysis has further corroborated the dominance of the CP-MLR identified descriptors.Applicability domain analysis revealed that the suggested models have acceptable predictability.All the compounds are within the applicability domain of the proposed models and were evaluated correctly.