Mutagenic evaluation of antischistosomal drugs and their derivatives inNeurospora crassa

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Abstract
The mutagenic activities of lucanthone, hycanthone, niridozole, and the indazole analogs of lucanthone (IA‐3 and IAS) 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.

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