Synthesis of a new nor-aza-steroidal ester of p-N,N-bis-(2-chloroethyl)aminophenylbutyric acid and in vitro study of its mutagenicity and clastogenicity.
A new nor-aza-steroidal ester of chlorambucil has been synthesized. The study of the mitotic index in CHO and HeLa cells treated with this compound showed that it may be a cytostatic drug. It was also found that treatment of CHO cells with a dose as low as 5 micrograms/ml induces a large number of sister chromatid exchanges. A great number of abnormal metaphases has been observed when CHO cells were treated with the compound at a dose of 25 micrograms/ml. When the compound was tested in the Ames/Salmonella microsome assay, it was found to be mutagenic in strains TA100 and TA1535, both with and without metabolic activation.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity*; D001378:Azasteroids / Q000138:chemical synthesis / Q000633:toxicity*; D002273:Carcinogens; D002478:Cells, Cultured; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D008677:Metaphase / Q000187:drug effects; D009153:Mutagens; D051381:Rats; D013260:Steroids, Heterocyclic / Q000633:toxicity*
D000970:Antineoplastic Agents; D001378:Azasteroids; D002273:Carcinogens; D009153:Mutagens; D013260:Steroids, Heterocyclic; C051252:17-hydroxy-4-aza-A-nor-5-androsten-3-one (4-N,N-bis(2-chloroethylamino)phenyl)butyrate; D002699:Chlorambucil