title: Thiophene analogues of the carcinogens benzidine and 4-aminobiphenyl: evaluation in vitro.
abstract: A biologically active molecule with one or more aromatic rings often retains its activity when one of these rings is replaced by an isosteric and/or isoelectronic aromatic ring. Consideration has been given to whether this effect can be expected to apply to aromatic organic carcinogens. The literature relevant to this topic has been reviewed and the thiophene analogues of the carcinogens benzidine and 4-aminobiphenyl have been synthesized and evaluated for potential carcinogenicity. The compounds prepared were 5-p-acetamidophenyl-2-thiophenamine hydrochloride (XIII), 5-phenyl-2-thiophenamine hydrochloride (XIV), N-(5-p-acetamido-phenylthiophen-2-yl)acetamide (XV) and N-(5-phenylthiophen-2-yl)-acetamide (XVI) (see Chart for structures). Each compound was evaluated in the Salmonella reverse-mutation assay of Ames and the cell-transformation assay of Styles. The activity profiles observed for these compounds in vitro were consistent with their known chemistry, and indicate potential carcinogenicity. However, their overall chemical and biological behaviour casts doubt upon whether they would be capable of eliciting tumours in vivo. Because it is important to establish the degree of reliance which can be placed upon in vitro predictions of potential carcinogenicity generated for structurally new compounds, one of the thiophene derivatives, N-(5-phenylthiophen-2-yl)acetamide ((XVI), is currently being evaluated for carcinogenicity in mice.
mesh_terms: D000611:Aminobiphenyl Compounds / Q000494:pharmacology*; D001560:Benzidines / Q000494:pharmacology*; D002273:Carcinogens; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D009154:Mutation / Q000187:drug effects; D012475:Salmonella / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000611:Aminobiphenyl Compounds; D001560:Benzidines; D002273:Carcinogens; D013876:Thiophenes