title: Quantitative structure--activity relationships of antimutagenic benzalacetones and 1,1,1-trifluoro-4-phenyl-3-buten-2-ones.
abstract: The antimutagenic activities (IC(50)) of benzalacetones (BZ) and 1,1,1-trifluo-4-phenyl-3-buten-2-ones (TF) against UV-induced mutagenesis in Escherichia coli WP2s(uvrA trpE) were quantitatively analyzed in terms of physicochemical parameters by regression analyses. Structural requirements for maximal potency were derived from the results of quantitative structure--activity relationship (QSAR) analyses: (1) ring substituents should be electron-withdrawing; (2) 2-OH substituents incapable of intramolecular hydrogen-bonding notably increase the potency; and (3) replacement of CH(3) group by CF(3) in the side chain enhances the activity. Contrary to our expectations, the best correlation lacked hydrophobic effects. Antimutagenic activities against gamma-induced mutagenesis in Salmonella typhimurium TA2638 were also studied for some derivatives in the BZ series, where, in addition to electronic and hydrogen-bonding factors, a hydrophobic term was also significant. Physicochemical meanings of the derived correlations are discussed.
authors.affiliation: Kobe Pharmaceutical University, Motoyamakita-machi, Higashinadaku, Kobe 658-8558, Japan. yamagami@kobepharma-u.ac.jp
authors.forename: Chisako
authors.initials: C
authors.lastname: Yamagami
authors.forename: Noriko
authors.initials: N
authors.lastname: Motohashi
mesh_terms: D016587:Antimutagenic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002074:Butanones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics / Q000528:radiation effects; D005720:Gamma Rays; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D016296:Mutagenesis / Q000528:radiation effects; D021281:Quantitative Structure-Activity Relationship; D014466:Ultraviolet Rays
chemical_list: D016587:Antimutagenic Agents; D002074:Butanones