In vitro antimycobacterial activities of 2'-monosubstituted isonicotinohydrazides and their cyanoborane adducts.
As a result of our search for new isoniazid derivatives with extended spectra of activity, we evaluated the in vitro antimycobacterial activities of isonicotinohydrazides (compounds 2) and their cyanoborane adducts (compounds 3), both obtained by the reaction of isonicotinoylhydrazones (compounds 1) with sodium cyanoborohydride. Most of the tested compounds displayed moderate to high activity against Mycobacterium tuberculosis H37Rv, with MICs ranging from 0.2 to 12.5 microg/ml. In particular, some hydrazides showed activity similar to that of rifampin (MIC = 0.2 microg/ml) and rather low cytotoxicity, so that they were generally shown to possess high safety indices. In contrast, the coordination to a cyanoborane (BH(2)CN) group (compounds 3) in general brought about a decrease in antimycobacterial activity, while cytotoxicity increased. Interestingly, selected compounds 1 to 3, mostly hydrazides (compounds 2), were effective in killing M. tuberculosis growing within macrophages at concentrations in culture medium which were much lower than the corresponding MICs. These compounds also displayed good activity against drug-resistant M. tuberculosis strains.
Maccari
Rosanna
R
Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università di Messina, 98168 Messina, Italy. rmaccari@pharma.unime.it
Ottanà
Rosaria
R
Monforte
Francesca
F
Vigorita
Maria Gabriella
MG
D000995:Antitubercular Agents / Q000494:pharmacology*; D001880:Boranes / Q000494:pharmacology*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
D000995:Antitubercular Agents; D001880:Boranes; D007538:Isoniazid