Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

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QSAR Studies of Non-Nucleoside Reverse Transcriptase Inhibitors: The Hydrophobic Effect

Author(s): L. Douali, D. Cherqaoui.

Abstract:

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are promising compounds in the search for potent and selective drugs for the treatment of AIDS. Although they are structurally diverse, the NNRTIs exhibit a striking similarity in their mode of action on the reverse transcriptase (RT) hydrophobic pocket. Several quantitative structure-activity relationship (QSAR) studies have been devoted to the HEPT and TIBO derivatives acting as NNRTIs. Thanks to their ability to perform non-linear mapping of the physicochemical descriptors to the corresponding biological activity, neural networks (NNs) proved to be a powerful QSAR modeling technique for this series of inhibitors. They show the importance of hydrophobic character of these compounds in their anti-HIV activity variation. One of the purposes of QSAR analyses is to understand the forces governing the activity of a particular class of compounds and to assist drug design. The present work rationalizes in depth the relationship between the hydrophobic character of NNRTIs and their anti-HIV activity. The variation of anti-HIV activity with respect to the hydrophobic parameters is performed by means of NNs and its non-linear aspect is discussed. There is a similarity in the hydrophobic character of TIBO and HEPT derivatives.

Keywords: QSAR, hydrophobicity, non-linear, neural networks, anti-HIV, NNRTIs, HEPT, TIBO

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Article Details

VOLUME: 2
ISSUE: 1
Year: 2006
Page: [21 - 29]
Pages: 9
DOI: 10.2174/157340906776056446