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论文类型：期刊论文

发表时间：2008-10-01

发表刊物：QSAR & COMBINATORIAL SCIENCE

收录刊物：SCIE、Scopus

卷号：27

期号：10

页面范围：1183-1192

ISSN号：1611-020X

关键字：Catechol-O-methyltransferase; Inhibitor; 3-D QSAR; CoMFA; CoMSIA

摘要：Inhibitors of Catechol-O-Methyltransferase (COMT) play an important role in the treatment of Parkinson's Disease (PD). A new Three-Dimensional Quantitative Structure-Activity Relationship (3-D QSAR) analysis was performed oil 36 previously reported COMT inhibitors employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methodologies to correlate the Molecular fields and percent inhibition values and three predictive models were derived. The CoMFA and CoMSIA models with steric and electrostatic field yielded cross-validated r(cv)(2)s of 0.585 and 0.528, respectively whereas the conventional r(ncv)(2)S Were 0.979 and 0.891. respectively. The CoMSIA model with hydrophobic field exhibited a r(cv)(2) of 0.544 and a r(ncv)(2) of 0.930. The individual inspection of 3-D contours generated from these models helps in understanding the possible region for structural modification of Molecules to improve the inhibitory bioactivity. These 3-D QSAR models are also Useful for designing and predicting novel COMT inhibitors.