| Design of nevirapine derivatives insensitive to the K103N and Y181C HIV-1 reverse transcriptase mutants. | |
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MedLine Citation:
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PMID: 16644557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nevirapine (Viramune) belongs to the first generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Its efficiency is limited by drug resistant mutations, such as K103N and Y181C, so, the aim of this work was to design novel nevirapine analogues insensitive to the K103N and Y181C HIV-1 RT. 360 Nevirapine derivatives were designed using a combinatorial library design approach and these compounds were docked into the binding pocket of mutant HIV-1 RT enzyme structures, using the GOLD program. 124 Compounds having a GoldScore higher than that of nevirapine (55.00 and 52.00 for K103N and Y181C mutants, respectively) were first retrieved and submitted to a topological analysis with the SILVER program. Consequently, 31 compounds presenting a significant percentage of the surfaces buried upon binding (>80%) and exhibiting hydrogen bonds to either N103 or C181 residues of the HIV-RT were selected. To ensure that these compounds had hydrogen bonding interaction to either N103 or C181 residues, their interaction energies were estimated by quantum chemical calculations (QCCs). Finally, QCCs represent an alternative method for performing post docking procedure. |
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Authors:
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P Saparpakorn; S Hannongbua; D Rognan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: SAR and QSAR in environmental research Volume: 17 ISSN: 1062-936X ISO Abbreviation: SAR QSAR Environ Res Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-04-28 Completed Date: 2006-07-18 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9440156 Medline TA: SAR QSAR Environ Res Country: England |
Other Details:
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Languages: eng Pagination: 183-94 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-HIV Agents
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chemistry* Combinatorial Chemistry Techniques Drug Design Drug Resistance HIV Reverse Transcriptase / genetics* Mutation* Nevirapine / analogs & derivatives, chemistry* Reverse Transcriptase Inhibitors / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Reverse Transcriptase Inhibitors; 129618-40-2/Nevirapine; EC 2.7.7.49/HIV Reverse Transcriptase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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