ELECTRONIC-PROPERTIES ON N-HETEROAROMATICS .67. RELATIONSHIP OF CARCINOGENICITY, MUTAGENICITY, AND K-REGION REACTIVITY IN BENZ[C]ACRIDINES

  • 1 January 1979
    • journal article
    • research article
    • Vol. 70  (6) , 749-754
Abstract
Benz[c]acridine and its 10 methyl-substituted derivatives were examined for chemical reactivity with osmium tetroxide and mutagenic activity on Salmonella typhimurium, and the results were contrasted with the electronic charge in the K region and the carcinogenic activity of benz[c]acridines. The addition of osmium tetroxide took place at the K region of benz[c]acridines. A linear relationship was established between the charge in the K region and the rate constant of the 2nd-order reaction between osmium tetroxide and benz[c]acridines, except the 5,7-dimethyl derivative whose substituent in the 5-position sterically hindered the reaction. Benz[c]acridines showed mutagenic activity in the presence of S-9 Mix but not in the absence of S-9 Mix. There was a corresponding relationship among the K-region reactivity, mutagenic activity and carcinogenic activity in benz[c]acridines. The only exception for this was the 7,11-dimethyl derivative in which the 11-methyl group had a steric effect on the ring-nitrogen atom. Apparently, a common mechanism with regard to the reactivity of the K region is working in carcinogenesis and mutagenesis. Benz[c]acridines probably are activated, before displaying carcinogenic or mutagenic activity, to a proximate form such as 5,6-epoxides, through a metabolic process in which the nucleophilic property of the K region to react with electrophilic reagents plays an important role.

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