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2,3-Dihydro-6,7-dihydroxy-1H-isoindol-1-one-Based HIV-1 Integrase Inhibitors

Year: 2007

Type: article

Abstract: The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1 H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm070715d

Authors: Xue Zhi Zhao, Elena A. Semenova, B. Christie Vu, Kasthuraiah Maddali, Christophe Marchand, Stephen H. Hughes, Yves Pommier, Terrence R. Burke

Institutions: National Institutes of Health, Frederick National Laboratory for Cancer Research, National Cancer Institute, Center for Cancer Research

Language: English

Topic: HIV/AIDS drug development and treatment

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

Open Access status: green

Funder: National Institutes of Health

OpenAlex ID: W2005569801

FWCI: 1.573

Cites: 34

Cited by: 51

Related to: 10