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DETERMINING THE STRUCTURE-ACTIVITY RELATIONSHIPS OF AMINOBIPHENYL AND BENZIDINE ANALOGS
Citation:
Chung, K. T. AND L D. Claxton. DETERMINING THE STRUCTURE-ACTIVITY RELATIONSHIPS OF AMINOBIPHENYL AND BENZIDINE ANALOGS. Presented at 10th International Congress of Toxicology, Tampere, Finland, July 11-16, 2004.
Description:
Determining the structure-activity relationships of aminobiphenyl and benzidine analogues
Benzidine is a confirmed human carcinogen causing bladder and other types of cancer in humans and animals. Many of the benzidine and related aminobiphenyl compounds are mutagenic in the Salmonella /microsome mutagenicity assay. Reanalysis of the mutagenicity data from the literature for 40 benzidine/aminobiphenyl analogues was done using the GeneTox Manager software. For TA98, 4,4'-dinitro-2-biphenylamine, 3-nitrobenzidine, 3,3'-dichlorobenzidine, 4amino-4'-nitrobiphenyl, 3,3'-dibromobenzidine, 3, 3'-difluoroebenzidine, 3,3'-dinitrobenzidine, 2nitrobenzidine, 4-amino-4'-hydroxybiphenyl and 3,3'-dimethoxybenzidine were mutagenic without exogenous mammalian activation (S9). For TA100, only 4,4'-dinitro-2-biphenylamine, 3nitrobenzidine and 3,3'-dibromobenzidine were direct mutagens. Many other analogues were mutagenic but exogenous mammalian activation (S9) is required for both strains TA98 and TA 100. We also found that the addition of sulfonic acid moiety to the molecule of benzidine reduced the mutagenicity. Substitutions of an alkyl group on the ortho position to amino group also influenced the mutagenicity. Some physicochemical parameters such as the lowest unoccupied molecular orbital energy (Elumo) highest occupied molecular orbital energy (EHOMO) and hydrophobiocity appeared to be important parameters that correlate with mutagenicity.