Mutagenic evaluation of antischistosomal drugs and their derivatives in Neurospora crassa.
The mutagenic activities of lucanthone, hycanthone, niridazole, and the indazole analogs of lucanthone (IA-3 and IA-5) or hycanthone (IA-4 and IA-6) were studied by assaying for the induction of specific locus mutations in the ad-3 region of N. crassa. The results show that lucanthone, hycanthone, and their indazole analogs (IA-3 through IA-6) are all mutagenic in N. crassa when conidia are treated with any of these compounds. On a per mole basis, hycanthone is the least toxic and mutagenic, whereas IA-3 is the most toxic and mutagenic compound among the six closely related agents. In general, compounds with a methyl group at the C-4 position are more mutagenic than compounds with a methanol group; 6-chloroindazole analogs are more mutagenic and more toxic than nonchlorinated analogs. Niridazole is not mutagenic when conidial suspensions are treated. However, the mutation frequency increased more than 50-fold when niridazole was added to the medium used to grow vegetative cultures. Thus, it appears that the mutagenic activity of this latter compound requires metabolic activation.
D006826:Hycanthone / Q000494:pharmacology; D008154:Lucanthone / Q000494:pharmacology; D009153:Mutagens; D009154:Mutation / Q000187:drug effects; D009491:Neurospora / Q000187:drug effects*; D009492:Neurospora crassa / Q000187:drug effects* / Q000254:growth & development; D012556:Schistosomicides / Q000494:pharmacology*
D009153:Mutagens; D012556:Schistosomicides; D006826:Hycanthone; D008154:Lucanthone