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 ≃ B ≫ C > D > 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 > B > A ≥ E ≃ D.

The two compounds tested for in vitro transformation, Compounds A and B, demonstrated a positive effect in both the C3H10T½ 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.

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This investigation was supported in part by European Communities Commission [Contract CEE-ENV, 545 F (RS) and INSERM Grant 813021 CRL.

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©1984 American Association for Cancer Research.
1984
Cancer Research, Inc.