title: Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors.
abstract: 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.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Laith Q
authors.initials: LQ
authors.lastname: Al-Mawsawi
authors.forename: Raveendra
authors.initials: R
authors.lastname: Dayam
authors.forename: Laleh
authors.initials: L
authors.lastname: Taheri
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: 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
chemical_list: D003603:Cytotoxins; D019428:HIV Integrase Inhibitors; D006834:Hydrazines; C000687:salicyl hydrazide; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1