AIM: Inhibitors of catechol-O-methyltransferase (COMT) have always been administered to improve the bioavailability of L-Dopa in the treatment of Parkinson disease (PD). A new three-dimensional quantitative structure-...AIM: Inhibitors of catechol-O-methyltransferase (COMT) have always been administered to improve the bioavailability of L-Dopa in the treatment of Parkinson disease (PD). A new three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis is performed to correlate the molecular fields with percent inhibition values. METHODS: Three predictive models were derived based on 36 previously reported COMT inhibitors employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodologies. RESULTS: The CoMFA model and CoMSIA model with steric and electrostatic field yielded cross-validated rcv2 0.585 and 0.528 respectively, whereas the conventional rncv2 were 0.979 and 0.891. The CoMSIA model with hydrophobic field exhibited rcv2 0.544 and rncv2 0.930. CONCLUSION: The derived models from CoMFA and CoMSIA all exhibit good prediction for both internal and external validations. The individual inspection of 3D contours generated from these models helps in understanding the possible region for structural modification of molecules to improve the inhibitory bioactivity. The 3D-QSAR models may be useful in designing and predicting novel COMT inhibitors.展开更多
HMG-CoA reductase converts HMG-CoA to mevalonate,with this catalysis constituting a committed step in the biosynthesis of cholesterol.So,it’s primary drone in treatment coronary artery disease.At present,several stat...HMG-CoA reductase converts HMG-CoA to mevalonate,with this catalysis constituting a committed step in the biosynthesis of cholesterol.So,it’s primary drone in treatment coronary artery disease.At present,several statins are available in the drug market,however,up to now the quantitative structure-activity relationship of all of known inhibitors hasn’t been reported.In order to provide a theoretical guide for the synthesis of novel inhibitors,the quantitative structure-activity relationship of the inhibitors of HMG-CoA reductase were performed by using 3D-QSAR approach: comparative molecular field analysis(CoMFA).The computed obtained CoMFA model with(q^2=0.4,) r^2=0.955,SE=0.110,F=85.335.It not only can be used to explain the structure-activity relationship of compound but also has powerful predictive ability.展开更多
文摘AIM: Inhibitors of catechol-O-methyltransferase (COMT) have always been administered to improve the bioavailability of L-Dopa in the treatment of Parkinson disease (PD). A new three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis is performed to correlate the molecular fields with percent inhibition values. METHODS: Three predictive models were derived based on 36 previously reported COMT inhibitors employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodologies. RESULTS: The CoMFA model and CoMSIA model with steric and electrostatic field yielded cross-validated rcv2 0.585 and 0.528 respectively, whereas the conventional rncv2 were 0.979 and 0.891. The CoMSIA model with hydrophobic field exhibited rcv2 0.544 and rncv2 0.930. CONCLUSION: The derived models from CoMFA and CoMSIA all exhibit good prediction for both internal and external validations. The individual inspection of 3D contours generated from these models helps in understanding the possible region for structural modification of molecules to improve the inhibitory bioactivity. The 3D-QSAR models may be useful in designing and predicting novel COMT inhibitors.
文摘HMG-CoA reductase converts HMG-CoA to mevalonate,with this catalysis constituting a committed step in the biosynthesis of cholesterol.So,it’s primary drone in treatment coronary artery disease.At present,several statins are available in the drug market,however,up to now the quantitative structure-activity relationship of all of known inhibitors hasn’t been reported.In order to provide a theoretical guide for the synthesis of novel inhibitors,the quantitative structure-activity relationship of the inhibitors of HMG-CoA reductase were performed by using 3D-QSAR approach: comparative molecular field analysis(CoMFA).The computed obtained CoMFA model with(q^2=0.4,) r^2=0.955,SE=0.110,F=85.335.It not only can be used to explain the structure-activity relationship of compound but also has powerful predictive ability.
