doiSerbia

MTD-comsia modelling of HMG-CoA reductase inhibitors

Duda-Seiman Daniel M. (Department of Medical Ambulatory, Medical Emergencies, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania)
Speranţa Avram (Department of Physiology and Biophysics, University of Bucharest, Faculty of Biology, Bucharest, Romania)
Mancaş Silvia (Department of Medical Ambulatory, Medical Emergencies, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania)
Careja Valentin (Institute of Chemistry “Coriolan Drăgulescu” of the Romanian Academy, Timisoara, Romania)
Duda-Seiman Corina (Department of Chemistry, University of West Timisoara, Faculty of Chemistry-Biology-Geography, Timişoara, Romania)
Putz Mihai V. (Department of Chemistry, University of West Timisoara, Faculty of Chemistry-Biology-Geography, Timişoara, Romania)
Ciubotariu Dan (Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babeş”, Timisoara, Timisoara, Romania)

The 3D quantitative structure-activity relationship for a series of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors based on the pyrrolylethyl-tetrahydropyranone scaffold was examined using the Minimal Topological Difference (MTD) method and comparative molecular similarity index analysis (CoMSIA). The studied compounds were of the tetrahydro-4-hydroxy-6-[2-(1H)-pyrrol-1-yl]ethyl-2H-pyran-2-one type. In clinical practice, HMG-CoA reductase inhibitors are usually referred to by the generic name statins. The analysis performed using the MTD method showed that voluminous substituents produce a significant biological activity ( 2 R2CV=0.677>0.5; SEECV=0.319 ), while the CoMSIA method added useful information regarding the influence of the steric, electrostatic, hydrophobic, hydrogen bond donor, and acceptor properties on biological activity (R2CV=0.60; r2=0.98).

Keywords: statins, molecular modelling, correlations, 3D-quantitative structure-biological activity