Mutagenicity of new analogs of 5-nitrofurans

Journal Article · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6989366

Hatcher, J F; Ichikawa, M; Bryan, G T; Swaminathan, S

The authors reported earlier the synthesis of methyl 3,4-diphenyl-5-nitro-2-furoate (I) and a number of its reduction products. They extended this synthesis to obtain 3,4-diphenyl substituted analogs of established carcinogenic 5-nitrofuryl thiazoles. They report the mutagenic activities of this new series of furan analogs: methyl 3,4-diphenyl-2-furoate (II), 3,4-diphenyl-5-nitro-2-acetylfuran (III), 3,4-diphenyl-5-nitro-2-bromoacetylfuran (IV), 2-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole (V) and 2-acetylamino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole (VI) using nitroreductase-proficient (TA100 and TA98) and deficient (TA100NR and TA98NR) strains. All the nitro analogs (I, III, IV, V, and VI) were active (114, 31, 70, 3 and 9 rev/nmole) in TA100 while the non-nitro analog (II) was inactive. In TA98, I and III had 15-fold less activity relative to TA100. V and VI were inactive in TA98. Furthermore, I and III were less active in TA100NR and TA98NR compared to the response in the parent strains. In contrast, the bromo analog IV was equally active in TA100, TA98, TA100NR and TA98NR, suggesting alternate pathways of activation of this chemical. V and VI were about 4000-fold less active in TA100 than the carcinogenic analogs lacking the phenyl substituents. These results demonstrate that for mutagenic activity the nitro group is essential and the potency of activity is influenced by the substituents at the 2-position of furan.

• Research Organization: Wisconsin Clinical Cancer Center, Madison
• OSTI ID: 6989366
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
NITRO COMPOUNDS
MUTAGEN SCREENING
BIOLOGICAL VARIABILITY
FURANS
MUTAGENESIS
HETEROCYCLIC COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
SCREENING
560300* - Chemicals Metabolism & Toxicology