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ABSTRACTAs 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 tuberculosisH37Rv, with MICs ranging from 0.2 to 12.5 μg/ml. In particular, some hydrazides showed activity similar to that of rifampin (MIC = 0.2 μg/ml) and rather low cytotoxicity, so that they were generally shown to possess high safety indices. In contrast, the coordination to a cyanoborane (BH2CN) 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. tuberculosisgrowing 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. tuberculosisstrains.

Diastereomers of antiinflammatoryanalgesic and antihistaminic 3,3′1,2ethanediylbis2aryl4thiazolidinone derivatives possessing two stereogenic centers indicated as BIS 2C have been widely investigated in recent years. The 5,5′dimethyl analogues BIS 4C, now reported, have been synthesized by reaction of ± αmercaptopropionic acid and N,Ndi3fluorobenzylidenethylenediamine. Because the 2 and 2′carbons bear the same groups and similarly the 5 and 5′ carbons, and the latter groups are different from the former, four enantiomeric pairs and two mesoforms exist in this situation. These diastereomers were identified by the concerted use of nmr spectroscopy and hplc on chiral stationary phase.

The synthesis of isonicotinohydrazide mono- and di-cyanoborane adducts 2 and 3 by reaction of isonicotinoylhydrazones 1 and sodium cyanoborohydride, their characterization (MS, IR, 1H, 13C and 11~B NMR) and experimental conditions of the reaction course have been investigated and discussed.

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