Bioorganic & Medicinal Chemistry Letters 2007-12-01

Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors.

Laith Q Al-Mawsawi, Raveendra Dayam, Laleh Taheri, Myriam Witvrouw, Zeger Debyser, Nouri Neamati

Index: Bioorg. Med. Chem. Lett. 17(23) , 6472-5, (2007)

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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.