X-ray and molecular modelling in fragment-based design of three small quinoline scaffolds for HIV integrase inhibitors

被引：16

作者：

Majerz-Maniecka, Katarzyna ^{[1
]}

Musiol, Robert ^{[2
]}

Skorska-Stania, Agnieszka ^{[1
]}

Tabak, Dominik ^{[2
]}

Mazur, Pawel ^{[2
]}

Oleksyn, Barbara J. ^{[1
]}

Polanski, Jaroslaw ^{[2
]}

机构：

[1] Jagiellonian Univ, Fac Chem, PL-30060 Krakow, Poland

[2] Univ Silesia, Inst Chem, PL-40007 Katowice, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 05期

关键词：

HIV integrase; Quinolines; Fragment-based drug design; Crystal structure; BIOLOGICAL-ACTIVITY SPECTRUM; BINDING MODE; DRUG DESIGN; STREPTONIGRIN; LAVENDAMYCIN; STYRYLQUINOLINES; REPLICATION; MECHANISM; CRYSTAL; LESSONS;

D O I：

10.1016/j.bmc.2011.01.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Crystal structures of three small molecular scaffolds based on quinoline, 2-methylquinoline-5,8-dione, 5-hydroxy-quinaldine-6-carboxylic acid and 8-hydroxy-quinaldine-7-carboxylic acid, were characterised. 5-Hydroxy-quinaldine-6-carboxylic acid was co-crystallized with cobalt(II) chloride to form a model of divalent metal cation-ligand interactions for potential HIV integrase inhibitors. Molecular docking into active site of HIV IN was also performed on 1WKN PDB file. Selected ligand-protein interactions have been found specific for active compounds. Studied structures can be used as scaffolds in fragment-based design of new potent drugs. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1606 / 1612

页数：7

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