New chloro, fluorobenzylindole derivatives as integrase strand-transfer inhibitors (INSTIs) and their mode of action

被引：18

作者：

Ferro, Stefania ^{[1
]}

De Luca, Laura ^{[1
]}

Barreca, Maria Letizia ^{[2
]}

De Grazia, Sara ^{[1
]}

Christ, Frauke ^{[3
,4
]}

Debyser, Zeger ^{[3
,4
]}

Chimirri, Alba ^{[1
]}

机构：

[1] Univ Messina, Dipartimento Farmacochim, I-98168 Messina, Italy

[2] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06123 Perugia, Italy

[3] Katholieke Univ Leuven, B-3000 Louvain, Flanders, Belgium

[4] IRC KULAK, B-3000 Louvain, Flanders, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 15期

关键词：

HIV-1; integrase; Induced-fit docking; Integrase strand-transfer inhibitors; Microwave-assisted organic synthesis; REVERSE-TRANSCRIPTASE INHIBITORS; ANTI-HIV ACTIVITY; BINDING MODE; TN5; TRANSPOSASE; RALTEGRAVIR; UPDATE; POTENT; SITE; MECHANISM; DISCOVERY;

D O I：

10.1016/j.bmc.2010.06.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The life cycle of HIV-1 requires extensive assistance from the integrase (IN) enzyme which therefore constitutes an attractive therapeutic target for the development of anti-AIDS agents. We herein report the synthesis and biological evaluation of new HIV integrase strand-transfer inhibitors (INSTIs) which proved to be also potent anti-HIV agents. The binding mode of the most representative molecules were also studied by induced-fit docking (IFD). The obtained IFD results were consistent with the mechanism of action proposed for this class of IN inhibitors, that is metal chelating/binding agents. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

引用

页码：5510 / 5518

页数：9

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