Mutagenicity of nitrobenzyl derivatives: potential bioreductive anticancer agents.
Ortho-, meta- and para-nitrobenzyl bromides, alcohols, ethers and esters were synthesised and tested for their mutagenicity toward Salmonella typhimurium TA100, TA100NR (nitroreductase deficient) and TA98 in absence of S9 mix and in TA100 with S9 mix. Compounds of the ortho- and meta-series were non mutagenic with and without S9 mix. Except for the alcohol and ether, the compounds of the para-series were mutagenic in TA100 with activity sequence propionate > butyrate > benzoate > acetate > bromide and this specific activity was reduced considerably by S9 mix. The Ames Salmonella test system does not seem to be an appropriate model to evaluate mutagenicity of o-nitrobenzyls. However, further work is in progress to test all the compounds for mutagenicity in mammalian system.
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
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Juneja
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Bala
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Kumar
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Gupta
D000438:Alcohols / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D001593:Benzyl Compounds / Q000737:chemistry / Q000633:toxicity*; D001965:Bromides / Q000737:chemistry / Q000633:toxicity; D015687:Cell Hypoxia; D004952:Esters / Q000737:chemistry / Q000633:toxicity; D004987:Ethers / Q000737:chemistry / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D008968:Molecular Conformation; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009578:Nitrobenzenes / Q000737:chemistry / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000438:Alcohols; D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D001965:Bromides; D004952:Esters; D004987:Ethers; D009153:Mutagens; D009578:Nitrobenzenes