Stereocontrolled synthesis of the four 16-hydroxymethyl-19-nortestosterone isomers and their antiproliferative activities

Schneider, Gyula and Kiss, Anita and Mernyák, Erzsébet and Benke, Zsanett and Wölfling, János and Frank, Éva and Bózsity, Noémi and Gyovai, András and Minorics, Renáta and Zupkó, István (2016) Stereocontrolled synthesis of the four 16-hydroxymethyl-19-nortestosterone isomers and their antiproliferative activities. STEROIDS, 105. pp. 113-120. ISSN 0039-128X

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Novel 16-hydroxymethyl-19-nortestosterone diastereomers were prepared by Birch reduction from the corresponding 3-methoxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol isomers with known configurations. The synthetized compounds are 16α- and 16β-hydroxymethyl-substituted 19-nortestosterone and their 17α-epimers. To prepare 17α-19-nortestosterone, the Mitsunobu inversion reaction of 19-nortestosterone with different alkyl and aryl carboxylic acids was chosen. Desacylation of the new compounds by the Zemplén method yielded the required 17α-19-nortestosterone. The antiproliferative activities of the structurally related compounds were determined in vitro through microculture tetrazolium assays on a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines. The 17α epimer of 19-nortestosterone demonstrated considerable activity, selectively for HeLa cells, with a calculated IC50 of 0.65 μM. The reference compound, cisplatin, displayed an order of magnitude higher IC50 (12.4 μM). The cancer selectivity of 17α-19-nortestosterone was tested by MTT assay performed with noncancerous human fibroblast cell line MRC-5. The results indicated that 17α-19-nortestosterone selectively disturbs the viability of HeLa cells without greatly affecting other cancer cell types and intact fibroblasts.

Item Type: Article
Additional Information: Hatodik szerző: Nagyné Frank Éva
Uncontrolled Keywords: 19-Nortestosterone; 17a-19-Nortestosterone; Stereocontrolled synthesis; Birch reduction; Antiproliferative activity
Subjects: R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Depositing User: MTMT SWORD
Date Deposited: 01 Feb 2021 15:04
Last Modified: 01 Feb 2021 15:04

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