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Synthesis and in vitro antimicrobial and antitumoral screening of novel lipophilic isoniazid analogues. VI.

Various kinds of lipophilic analogues of isonicotinic acid hydrazide (Isoniazid) were synthesized and in vitro explored in a search for antimycobacterial agents with extended activity spectrum against pathogens responsible for the AIDS-associated diseases. The primary in vitro screening showed that a) isonicotinoylhydrazones 1a, 1b, 1d, 1e are more active than the parent drug against non-tubercular mycobacteria (MIC ranging between 0.5 and 4 micrograms/ml), b) isonicotinohydrazides 6b and 6e display interesting antibacterial activity on some Gram + and Gram-strains, and c) trifluoromethyl-containing compounds 1a and 2c inhibit the growth of several human tumor cell lines at doses between 10(-5) and 10(-6) M. On the contrary, none of the tested analogues significantly counteracts the cytopathogenicity induced by HIV and HSV viruses.