ABSTRACT
The matrix metalloproteinase-13 (MMP-13) inhibitory activities of carboxylic acid based compounds, in presence and absence of bovine serum albumin (BSA), have been analyzed quantitatively in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models obtained through combinatorial protocol in multiple linear regression (CP-MLR) analysis and the participated descriptors in these models provided rationales to explain the inhibitory activities of these congeners. For MMP-13 inhibition activity, the identified descriptors (BEHm1, BELm1 and BEHm8) have highlighted the role of the atomic mass in terms of the highest and lowest eigenvalues derived from Burden matrix. The positive correlation with activity suggested that their higher values are desirable in improving the activity of a compound. Additionally, the descriptor C-027 representing R-CH-X type fragment in a molecular structure advocates the absence of such type of fragment for the improved activity. On the other hand presence of RCO-N< or >N-X=X type fragment (descriptor N-072) would be beneficiary to the MMP-13 inhibitory activity. The structural features, rationalized by the descriptors MSD (Balaban’s mean square distance index), nCrHR (number of ring tertiary C (sp3), H-047 (H attached to C1(sp3)/C0(sp2)) and H-050 (H attached to heteroatom) have imparted positive impact on the MMP-13 w/BSA inhibition activity. The atomic properties such as atomic polarizability and atomic Sanderson’s electronegativity have shown their positive impact on the activity via descriptors BELp4 and GATS3e in respective eigenvalues or lag. The other descriptors, MATS1m and MATS3e, have revealed the negative influence of atomic mass and electronegativity on the of MMP-13 w/BSA inhibition activity. The results obtained from CP-MLR analysis have been supported further through partial least-squares (PLS) study.
Subject(s)
Carboxylic Acids/analogs & derivatives , Carboxylic Acids/analysis , Carboxylic Acids/metabolism , Enzyme Inhibitors/chemistry , Linear Models , Matrix Metalloproteinase Inhibitors/analysis , Matrix Metalloproteinase Inhibitors/chemistry , Models, Chemical , Molecular Structure , Quantitative Structure-Activity RelationshipABSTRACT
Hydrophobic fragment constants (f) of benzotriazol-2-yl and Ar-N[CO-]2 systems, and aliphatic H/S polar interaction factors F(H/S) in Cl2CHCONH-Ar and Cl3CCONH-Ar, of Hansch and Leo's constructionist approach, were estimated as 0.69 (standard deviation = 0.17), -1.98, 0.95 and 0.98 respectively. The validity of the first constant has been tested by calculating the log P of compounds not included in the regression.
Subject(s)
Cyclopentanes/chemistry , Models, Theoretical , Molecular Structure , Regression Analysis , Reproducibility of Results , Triazoles/chemistryABSTRACT
Forty-four patients of meralgia paraesthetica presented with combination of symptoms mainly of numbness with loss of superficial sensation on the anterolateral aspect of a thigh were selected for the study. They responded well to local infiltration of hydrocortisone acetate and lignocaine hydrochloride which not only helped in diagnosis but also prevented the recurrence of symptoms in majority of cases.