QSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds.

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dc.contributor.authorSharma, B K
dc.contributor.authorSingh, P
dc.contributor.authorPrabhakar, Y S
dc.date.accessioned2015-09-09T07:38:32Z
dc.date.available2015-09-09T07:38:32Z
dc.date.issued2013-10
dc.description.abstractThe 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.en_US
dc.identifier.citationSharma B K, Singh P, Prabhakar Y S. QSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds. British Journal of Pharmaceutical Research. 2013 Oct; 3(4): 697-721.en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/163307
dc.language.isoenen_US
dc.source.urihttps://sciencedomain.org/abstract/1532en_US
dc.subjectMatrix metalloproteinase inhibitorsen_US
dc.subjectcarboxylic acid based compoundsen_US
dc.subjectchemometric descriptorsen_US
dc.subjectcombinatorial protocol in multiple linear regressionen_US
dc.subject(CP-MLR) analysisen_US
dc.subjectQSARen_US
dc.subject.meshCarboxylic Acids --analogs & derivatives
dc.subject.meshCarboxylic Acids --analysis
dc.subject.meshCarboxylic Acids --metabolism
dc.subject.meshEnzyme Inhibitors --chemistry
dc.subject.meshLinear Models
dc.subject.meshMatrix Metalloproteinase Inhibitors --analysis
dc.subject.meshMatrix Metalloproteinase Inhibitors --chemistry
dc.subject.meshModels, Chemical
dc.subject.meshMolecular Structure
dc.subject.meshQuantitative Structure-Activity Relationship
dc.titleQSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds.en_US
dc.typeArticleen_US
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