Chemistry and Structure-Activity Relationship of the Styrylquinoline-Type HIV Integrase Inhibitors

Molecules

Jean-François Mouscadet¹ 

[1] ¹LBPA, CNRS, Ecole Normale Supérieure de Cachan, France ²Faculté de Pharmacie, Université Paris-Sud, UMR CNRS 8076 BIOCIS, Châtenay-Malabry, France

关键词: AIDS;    HIV-1;    integrase;    inhibitor;    styrylquinoline;   

DOI  :  10.3390/molecules15053048

来源: mdpi

【 摘 要 】

In spite of significant progress in anti-HIV-1 therapy, current antiviral chemo-therapy still suffers from deleterious side effects and emerging drug resistance. Therefore, the development of novel antiviral drugs remains a crucial issue for the fight against AIDS. HIV-1 integrase is a key enzyme in the replication cycle of the retrovirus since it catalyzes the integration of the reverse transcribed viral DNA into the chromosomal DNA. Efforts to develop anti-integrase drugs started during the early nineties, culminating with the recent approval of Raltegravir. The discovery and the development of the styrylquinoline inhibitor class was an important step in the overall process. In this review we have described the key synthetic issues and the structure-activity relationship of this family of integrase inhibitors. Crystallographic and docking studies that shed light on their mechanism of action are also examined.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.