Mutagenicity of 3,4-diphenyl-5-nitrofuran analogs in Salmonella typhimurium

A new series of chemicals comprising eight different 3, 4-di-phenylsubstitutedfuran analogs, namely, methyl-3, 4-di-phenyl-2-furoate, methyl-3,4-diphenyl-5-nitro-2-furoate, 3, 4-diphenyl-5-nitro-2-furoicacid, 3, 4-diphenyl-5-nitro-2-acetylfuran, 3, 4-diphenyl-5-nitro-2-bromoacetylfuran,2-amino-4-(3, 4-diphenyl-5-nitro-2-furyl)thiazole, 2-acetyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole and 2-formyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole were synthesized and theirmutagenic activities tested in Salmonella typhi-murium. Thestructure—activity relationship studies revealed thatfor mutagenic activity the nitro group is essential and thatthe potency of activity is greatly altered by the nature ofthe substituent at the 2-position of the furan ring. The mutagenicactivities of these chemicals were generally much higher inTA100 compared to TA98. The relative order of activities for2-substituted, 3, 4-diphenyl-5-nitrofurans were COOCH₃ >COCH₂BR > COCH₃ > COOH in S. typhi-murium TA100. 3, 4-Diphenyl-5-nitro-2-bromoacetylfuranwas equally active in nitroreductase-proficient (TA98, TA100)and in nitroreductase-deficient (TA98NR, TA100NR) strains. Incontrast, the acetyl and carboxymethyl ester analogs were relativelyless active in nitroreductase-deficient strains. Mutagenic activitiesof 3, 4-diphenyl-substituted furylthiazoles in comparison withthe unsubstituted analogs of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide,N-[4-(5-nitro-2-furyl)-2-thiazolyl]-acetamide and 2-amino-4-(5-nitro-2-furyl)thiazolerevealed that the phenyl groups drastically reduced their mutagenicactivities. However, the relative order of activities formylamino<< acetylamino > amino were the same between phenyl-substitutedand unsubstituted analogs.