Abstract：
:We have investigated the toxicity of a series of 2-pyridylcarboxamidrazones in vitro using a rat liver metabolism system as well as human erythrocytes and mononuclear leucocytes (MNL) as target cells. Of the seven derivatives and four precursors tested, only minimal (<2.3%) metabolism-mediated methaemoglobin was formed by two analogues. However, one of these, a naphthylidene 2-pyridylcarboxamidrazone derivative (compound III), was also directly toxic to human MNLs. This toxicity was partially attenuated by the rat metabolising system and incubation of diethyldithiocarbamate or cimetidine together with compound III and the rat metabolising system suppressed the metabolism-dependent detoxification. This indicated that cytochrome P-450-mediated biotransformation of compound III was preventing its direct toxicity to the MNL. Of the seven derivatives tested, six were low in toxicity to MNL directly and in the presence of a metabolising system. The two compounds which were the most potent anti-mycobacterially, the dimethylpropyl and dimethylethyl benzylidene amidrazone derivatives, were also the least toxic to MNL and erythrocytes. This amidrazone series has shown promise for future development as antituberculosis drugs.
journal_name
Environ Toxicol Pharmacoljournal_title
Environmental toxicology and pharmacologyauthors
Coleman MD,Rathbone DL,Abberley L,Lambert PA,Billington DCdoi
10.1016/s1382-6689(98)00055-6subject
Has Abstractpub_date
1999-03-01 00:00:00pages
59-65issue
1eissn
1382-6689issn
1872-7077pii
S1382-6689(98)00055-6journal_volume
7pub_type
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