Discovery of N-aryl-naphthylamines as in vitro inhibitors of the interaction between HIV integrase and the cofactor LEDGF/p75

被引：17

作者：

Crucitti, Giuliana Cuzzucoli ^{[1
]}

Pescatori, Luca ^{[1
]}

Messore, Antonella ^{[1
]}

Madia, Valentina Noemi ^{[1
]}

Pupo, Giovanni ^{[1
]}

Saccoliti, Francesco ^{[1
]}

Scipione, Luigi ^{[1
]}

Tortorella, Silvano ^{[1
]}

Di Leva, Francesco Saverio ^{[3
]}

Cosconati, Sandro ^{[2
]}

Novellino, Ettore ^{[3
]}

Debyser, Zeger ^{[4
]}

Christ, Frauke ^{[4
]}

Costi, Roberta ^{[1
]}

Di Santo, Roberto ^{[1
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] Univ Naples 2, DiSTABiF, I-81100 Caserta, Italy

[3] Univ Naples Federico II, Dipartimento Farm, I-80131 Naples, Italy

[4] Katholieke Univ Leuven, Mol Med, Mol Virol & Gene Therapy, B-3000 Leuven, Flanders, Belgium

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 101卷

关键词：

Integrase; LEDGF/p75; LEDGINs; N-aryl-naphthylamine; SMALL-MOLECULE INHIBITORS; DERIVATIVES; DESIGN; AIDS; RESISTANCE; MECHANISM; GROWTH; DOMAIN; CELLS; SITE;

D O I：

10.1016/j.ejmech.2015.06.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-aryl-naphthylamines, exemplified by the structures 11-16, were chosen for an in-house library screening to assay their ability to disrupt the interaction between the LEDGF cofactor and the HIV integrase. Structure modification led also to design and synthesize new compounds 17a-f. Compounds 11e,h,k,n, 13b, and 14 showed good activity in AlphaScreen assay. The most active compound lie (IC50 = 2.5 mu M) was selected for molecular modeling studies and showed a binding mode similar to the one of the known LEDGIN 8. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：288 / 294

页数：7

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