Dataset Information

A QSAR Study of Matrix Metalloproteinases Type 2 (MMP-2) Inhibitors with Cinnamoyl Pyrrolidine Derivatives.

ABSTRACT: A multivariate PLS-QSAR study with a data set of 31 cinnamoyl pyrrolidine derivatives described as type 2 matrix metalloproteinases (MMP-2) inhibitors is presented in this paper. The variable selection was performed with the Ordered Predictors Selection (OPS) algorithm. The PLS model presented six descriptors and three Latent Variables (LV) that cumulated 71.845% of variance. Leave-N-out (LNO) cross validation and y-randomization tests showed that the model presented robustness and no chance correlation, respectively. The descriptors indicated that MMP-2 inhibition depends mainly on the electronic properties of the compounds. The model obtained can be useful as a support tool in the design of new MMP-2 inhibitors.

SUBMITTER: de Melo EB

PROVIDER: S-EPMC3383210 | biostudies-literature | 2012 Apr-Jun

REPOSITORIES: biostudies-literature

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A QSAR Study of Matrix Metalloproteinases Type 2 (MMP-2) Inhibitors with Cinnamoyl Pyrrolidine Derivatives.

de Melo Eduardo Borges EB

Scientia pharmaceutica 20120131 2

A multivariate PLS-QSAR study with a data set of 31 cinnamoyl pyrrolidine derivatives described as type 2 matrix metalloproteinases (MMP-2) inhibitors is presented in this paper. The variable selection was performed with the Ordered Predictors Selection (OPS) algorithm. The PLS model presented six descriptors and three Latent Variables (LV) that cumulated 71.845% of variance. Leave-N-out (LNO) cross validation and y-randomization tests showed that the model presented robustness and no chance cor ...[more]

PMID: 22896815

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Project description:Cardiac amyloidosis due to amyloid fibril deposition in the heart results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction disturbances. Immunoglobulin light chain-related CMP (AL-CMP) features rapidly progressive HF with an extremely poor prognosis compared with a CMP due to the deposition of mutant (ATTR) amyloidosis or wild-type (senile systemic amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition disrupts the myocardial extracellular matrix (ECM) homeostasis, which is partly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We therefore tested the hypothesis that circulating levels of MMPs and TIMPs in patients with AL-CMP and TTR-related CMP (TTR-CMP) are dissimilar and indicative of cardiac amyloid disease type.Fifty AL-CMP patients were compared with 50 TTR-CMP patients (composed of 38 SSA and 12 ATTR patients). Clinical and laboratory evaluations including echocardiography were performed at the initial visit to our center and analyzed. Serum MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were determined by ELISA. Compared with TTR-CMP patients, AL-CMP patients had higher levels of brain natriuretic peptide (BNP), troponin I (TnI), MMP-2, TIMP-1, and MMP-2/TIMP-2 ratio, despite less left ventricular (LV) hypertrophy and better preserved LV ejection fraction. Mortality was worse in AL-CMP patients than in TTR-CMP patients (log-rank P<0.01). MMP-2/TIMP-2 plus BNP and TnI showed the highest discriminative ability for distinguishing AL-CMP from TTR-CMP. Female sex (HR, 2.343; P=0.049) and BNP (HR, 1.041; P<0.01) were predictors for mortality for all patients with cardiac amyloidoses. Only BNP was a predictor of death in AL-CMP patients (HR, 1.090; P<0.01). There were no prognostic factors for all-cause death in TTR-CMP patients.Circulating concentrations of MMPs and TIMPs may be useful in differentiating patients with AL-CMP from those with TTR-CMP, resulting in earlier diagnostic vigilance, and may add prognostic information. In addition to an elevated BNP level, female sex increased the risk of death in patients with cardiac amyloidoses.

Dataset Information

A QSAR Study of Matrix Metalloproteinases Type 2 (MMP-2) Inhibitors with Cinnamoyl Pyrrolidine Derivatives.

Publications

A QSAR Study of Matrix Metalloproteinases Type 2 (MMP-2) Inhibitors with Cinnamoyl Pyrrolidine Derivatives.

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