Design of Anti-HIV Ligands by Means of Minimal Topological Difference (MTD) Method

1 Chemistry Department, West University of Timi soara, Pestalozzi Street No.16, Timi soara, RO-300115, Romania; E-mails: mvputz@cbg.uvt.ro and cori_mam@yahoo.com 2 Clinic of Preventive Cardiology and Cardiovascular Rehabilitation, University of Medicine and Pharmacy “Victor Babe s” Timi soara, B-dul C.D. Loga 49, RO-300020, Romania; E-mail: duda.seiman@cardiologie.ro 3 Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babe s” Timi soara, Bd. Eftimie Murgu No. 2, Timi soara, RO-300041, Romania; Email: ddragos@umft.ro, dciubotariu@mail.dnttm.ro 4 Faculty of Chemistry, “Politehnica” University Ti mi soara, Pia Ńa Victoriei no. 2, Timi soara, RO-300006, Romania; Email: medeleanu@chem.utt.ro 5 Institute of Chemistry “Coriolan Dr agulescu” of the Romanian Academy, Bd. Mihai Viteazul No. 24, RO-300223, Timisoara, Romania; Email: vcareja@acad-tim.utt.ro * Author to whom correspondence should be addressed. Received: 07 November 2006 / Accepted: 20 November 2006 / Published: 29 November 2006 Abstract: Molecular modeling and MTD methods are useful tools to assess both qualitative (SAR) and quantitative (QSAR) chemical structure-biological activity relationships. The 1-[(2-hydroxiethoxi)-methyl]-6-(phenylthio)thymine congeners (HEPT ligands) show in vitro anti-viral activity against the type-1 human immunodeficiency virus (HIV-1), which is the etiologic agent of AIDS. This work shows an extensive QSAR study performed upon a large series of 79 HEPT ligands using the MTD and HyperChem molecular modeling methods. The studied HEPT ligands are HIV reverse-transcriptase inhibitors. Their geometries were optimized and conformational analysis was carried out to build the hypermolecule, which allowed applying the MTD method. The hypermolecule was used for space mapping of the receptor’s interaction site. The obtained results show that there are three 3D molecular zones important for the anti-HIV biological activity of the HEPT ligands under study.