Collect. Czech. Chem. Commun. 2011, 76, 803-813
Published online 2011-06-15 11:29:17

QSAR study of a series of cholesteryl ester transfer protein inhibitors

Mahesh T. Chhabriaa, Bhanubhai N. Suhagiaa, Appaji B. Mandhareb and Pathik S. Brahmkshatriyaa,*

a Department of Pharmaceutical Chemistry, L M College of Pharmacy, Navrangpura, Ahmedabad-380 009, Gujarat, India
b Torrent Research Centre, Torrent Pharmaceuticals Ltd., Medicinal Chemistry-Drug Discovery, Gandhinagar-382 428, Gujarat, India


Cholesteryl ester transfer protein (CETP), an enzyme which catalyses the transfer of cholesteryl ester from HDL to VLDL, is a promising target for discovery of novel antihyperlipidemic agents due to its pivotal role in HDL metabolism and reverse cholesterol transport. Quantitative structure activity relationship study of a series of CETP inhibitors was carried out using genetic function approximation to study various structural requirements for CETP inhibition. Various lipophilic, electronic, geometric and spatial descriptors were correlated with CETP inhibitory activity. Developed models were found predictive as indicated by their good r2pred values and satisfactory internal and external cross-validation results. Study reveals that lipophilicity (ClogP), with parabolic relationship, contributed significantly to the activity along with some electronic, geometric and quantum mechanical descriptors. The present study can be applied to future lead optimization of CETP inhibitors.

Keywords: QSAR; Genetic function approximation; Molecular descriptors; Predictive models, Lack-of-fit; Medicinal chemistry; Drug design; Structure–activity relationships.

References: 29 live references.