کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5516603 | 1542682 | 2017 | 15 صفحه PDF | دانلود رایگان |
- Knorr reactions of steroidal β-ketoaldehydes with arylhydrazines were carried out.
- Pyrazole heteroring was introduced into rings D and A of the sterane core.
- Solvent and substituent effects on the regioisomeric distribution were investigated.
- Reactivity of the sterane precursors was compared.
- Antiproliferative effects were determined in vitro on human breast cancer cell lines.
Novel androstanopyrazoles have been efficiently synthesized from steroidal β-ketoaldehydes with different arylhydrazine hydrochlorides both under acidic and basic conditions. Knorr-type transformations of 16-hydroxymethylene-dehydroepiandrosterone containing its 1,3-dicarbonyl moiety on ring D, proved to be regioselective in pyridine at room temperature, while mixtures of regioisomers were obtained in acidic EtOH under reflux. Contrarily, the cyclocondensation reactions of 2-hydroxymethylene-dihydrotestosterone bearing its reactive functionalities on ring A, led to a mixture of pyrazole regioisomers in varying ratio depending on the applied medium. The regioisomeric distribution was found to depend on the electronic character of the substituent of the phenylhydrazine applied. After separating the related isomers by column chromatography, they were subjected to in vitro pharmacological studies to investigate their antiproliferative activities against three human breast malignant cell lines (MCF7, T47D, MDA-MB-231). Flow cytometry revealed that the most potent agents elicited a cell cycle disturbance on MDA-MB-231 and T47D cells.
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Journal: Steroids - Volume 126, October 2017, Pages 35-49