Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors.
The previously discovered salicylhydrazide class of compounds displayed potent HIV-1 integrase (IN) inhibitory activity. The development of this class of compounds as antiretroviral agents was halted due to cytotoxicity in the nanomolar to sub-micromolar range. We identified a novel class of non-cytotoxic hydrazide IN inhibitors utilizing the minimally required salicylhydrazide substructure as a template in a small-molecule database search. The novel hydrazides displayed low micromolar IN inhibitory activity and are several hundred-fold less cytotoxic than previously disclosed salicylhydrazide IN inhibitors.
Al-Mawsawi
Laith Q
LQ
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Dayam
Raveendra
R
Taheri
Laleh
L
Witvrouw
Myriam
M
Debyser
Zeger
Z
Neamati
Nouri
N
D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D016208:Databases, Factual; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology
D003603:Cytotoxins; D019428:HIV Integrase Inhibitors; D006834:Hydrazines; C000687:salicyl hydrazide; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1