Relationship between the chemical structure and the mutagenic and carcinogenic potentials of five naphthofurans.
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.
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
D002273:Carcinogens; D005663:Furans; D009153:Mutagens; D009281:Naphthalenes