MTD-CoMSIA modelling of HMG-CoA reductase inhibitors

作者：Duda Seiman Daniel M; Avram Speranta; Mancas Silvia; Careja Valentin; Duda Seiman Corina^*; Putz Mihai V; Ciubotariu Dan

来源：Journal of the Serbian Chemical Society, 2011, 76(1): 85-99.

DOI：10.2298/JSC100601019D

• statins
• molecular modelling
• correlations
• 3D-quantitative structure-biological activity

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 MID method showed that voluminous substituents produce a significant biological activity (R-CV(2) = 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 (R-CV(2) = 0.60; r(2) = 0.98).

• 出版日期2011