benzofurans and 2-nitro-7-methoxynaphtho(2-1b)furan

A series of benzofurans and naphthofurans was examined through the Salmonella/microsome assay. (i) With one possible exception, only 2-nitro derivatives give a mutagenic response. However, it appears that the mutagenic potency depends notably on the nature and the position of the other substituents in the molecule. (ii) The mutagenic response occurs in strains TA1537, TA1538, TA98 and TA100 but not in strain TA1535. Reversion of the missense mutation of TA1535 is thus induced only in presence of the plasmid pKM101. (iii) This mutagenic response is at least partially dependent on the bacterial nitroreductase activities and is usually lower in presence of activating mixture from rat liver. (iv) One of the compounds tested, 2-nitro-7-methoxynaphtho[2,1-b]furan (R7000), may be the most potent mutagen examined so far in the Salmonella/microsome assay. It yields about 200 000 revertants/nanomole on strain TA100 in the standard plate test. The relation between structure, mutagenic potency and other biological activities of the compounds are briefly discussed.

Topics: Benzofurans; Mutagenicity Tests; Mutagens; Nitrofurans; Salmonella typhimurium; Structure-Activity Relationship

The cytostatic effect of various derivatives of 2-nitro-naphthofurans has been determined in vitro on L1210 leukemia cells. A recently described new bio-assay (Discotest) was used, which consists in plating the cells in soft agarose and placing on top of the agarose layer a paper disc soaked with the compound to be tested. The halo of inhibition of colony formation which results from diffusion of the compound is proportional to the logarithm of the compound concentration. The most active derivatives were the 2-nitro-7-methoxy and 2-nitro-8-methoxy-naphtho[2,1-b] furans which are known to be highly bactericidal and protozoocidal.

Topics: Animals; Antineoplastic Agents; Benzofurans; Cells, Cultured; Chemical Phenomena; Chemistry; Culture Media; In Vitro Techniques; Leukemia L1210; Mice; Nitrofurans