Use of a Hexasubstituted Benzene Scaffold in the Development of Multivalent HIV-1 Integrase Inhibitors
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- Tupchiangmai Wipa
- Department of Chemistry, Faculty of Science, Chulalongkorn University
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- Choksakulporn Saowanaporn
- Department of Chemistry, Faculty of Science, Chulalongkorn University
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- Tewtrakul Supinya
- Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University
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- Pianwanit Somsak
- Department of Chemistry, Faculty of Science, Chulalongkorn University
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- Sritana-anant Yongsak
- Department of Chemistry, Faculty of Science, Chulalongkorn University
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The highly directional hexasubstituted benzene moiety was used as the central scaffold to create new human immunodeficiency virus (HIV)-1 integrase inhibitors through the attachment of multiple active groups. A series of potential inhibitors having substituted polyhydroxylated mono, bis and tris-cinnamoyl derivatives connected on the scaffold were prepared through Claisen–Schmidt condensations with substituted benzaldehydes, followed by partial demethylation to uncover the active phenolic groups required for the interactions with the integrase enzyme active sites. Using a multiplate integration assay method, four compounds carrying at least two sets of interacting moieties were found to be relatively potent integrase inhibitors with IC50 values in the low micromolar range. The results confirmed that multiple polyhydroxylated groups were required on the platform in order to effectively interact with the enzyme. The results from molecular docking studies consistently complemented the experimental results and revealed the nature of the potential key binding interactions responsible for the apparent activity of the active compounds.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 62 (8), 754-763, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204177183232
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- NII論文ID
- 130004677382
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- NII書誌ID
- AA00602100
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- COI
- 1:STN:280:DC%2BC2cbos1Crtw%3D%3D
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 025609791
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- PubMed
- 25087627
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可