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

International Journal of Molecular Sciences

Corina Duda-Seiman⁴  Daniel Duda-Seiman²  Dan Dragoş³  Mihai Medeleanu⁵  Valentin Careja¹  Mihai V. Putz⁴  Ana-Maria Lacrămă⁴  Adrian Chiriac⁴  Remus Nuţiu⁴ 

[1] Institute of Chemistry “Coriolan Drăgulescu” of the Romanian Academy, Bd. Mihai Viteazul No. 24, RO-300223, Timişoara, Romania;;Clinic of Preventive Cardiology and Cardiovascular Rehabilitation, University of Medicine and Pharmacy “Victor Babeş” Timişoara, B-dul C.D. Loga 49, RO-300020, Romania; E-mail:Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babeş” Timişoara, Bd. Eftimie Murgu No. 2, Timişoara, RO-300041, Romania;;Chemistry Department, West University of Timişoara, Pestalozzi Street No.16, Timişoara, RO-300115, Romania; E-mails:Faculty of Chemistry, “Politehnica” University Timişoara, Piaţa Victoriei no. 2, Timişoara, RO-300006, Romania;

关键词: anti-HIV Ligands;    Minimal Topological Difference (MTD) Method;    molecular design;   

DOI  :  10.3390/i7110537

来源: mdpi

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2006 by MDPI, (http://www.mdpi.org).