title: Relationship between the chemical structure and the mutagenic and carcinogenic potentials of five naphthofurans.
abstract: We have analyzed the relationship between the biological activities and chemical structure of five naphthofurans. The compounds studied included 2-nitro-7-methoxynaphtho[2,1-b]-furan (R 7000) (Compound A), 2-nitro-8-methoxynaphtho[2,1-b]-furan (Compound B), 2-nitronaphtho[2,1-b]furan (Compound C), 2-nitro-7-bromonaphtho[2,1-b]furan (Compound D), and 7-methoxynaphtho[2,1-b]furan (Compound E), the nonnitrated analogue of Compound A. The genotoxic activities of the compounds were studied in V79 cells using the micronucleus, sister chromatid exchange, and hypoxanthine-guanine phosphoribosyltransferase locus mutation tests. This allowed us to classify their mutagenic properties in the following order: A congruent to B much greater than C greater than D greater than E. However, in the in vivo short-term skin tests, the order in activities of the first three compounds is reversed, and the five compounds can be classified in decreasing rank of potency: C greater than B greater than A greater than or equal to E congruent to D. The two compounds tested for in vitro transformation, Compounds A and B, demonstrated a positive effect in both the C3H10T1/2 and the Syrian hamster embryo cell systems. The biological activities of Compounds A, B, C, and D appeared to be strongly linked to the presence of a NO2 group in position 2. These activities were enhanced or decreased by a methoxy group in position 7 or 8. Almost all activities were suppressed if the methoxy group in position 7 was replaced by a bromine (Compound D). The positive results obtained in the cell transformation assays and in the short-term skin tests indicate that Compounds A, B, and C are probably carcinogenic. Therefore, further in vivo studies should be accomplished before using the 2-nitronaphthofuran derivatives in human and animal treatments.
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004622:Embryo, Mammalian; D005260:Female; D005663:Furans / Q000633:toxicity; D005796:Genes / Q000187:drug effects; D008168:Lung; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009281:Naphthalenes / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D002273:Carcinogens; D005663:Furans; D009153:Mutagens; D009281:Naphthalenes