Oxazoline derivatives of [17(20)E]-21-norpregnene – inhibitors of CYP17A1 activity and proliferation of prostate carcinoma cells

• DOI: 10.1007/s11172-018-2122-7
• Publication Date: 2018-07-13T03:15:22Z
• Authors: V. A. Kostin; A. S. Latysheva; V. A. Zolottsev; Ya. V. Tkachev; V. P. Timofeev; A. V. Kuzikov; V. V. Shumyantseva; G. E. Morozevich; A. Yu. Misharin
• Keywords: CYP17A1; Oxazole; Oxazoline

Nine new oxazolinyl derivatives of [17(20)E]-21-norpregnene, differing in the structure of steroid moiety, were investigated for their potency to inhibit the CYP17A1 catalytic activity, as well as growth and proliferation of LNCaP and PC-3 prostate carcinoma cell lines. The activity of one of the investigated compounds, 2´-{[(E)3β-hydroxyandrost-5-en-17-ylidene]methyl}-4´,5´-dihydro-1´,3´-oxazole (1), was found to be comparable with that of Abiraterone, a known inhibitor of CYP17A1 used for treatment of prostate cancer. A model of the interaction of oxazoline 1 with the active site of CYP17A1 was constructed by the molecular dynamics method. A correlation was found between the structure and the biological activity in the series of [17(20)E]-21-norpregnene oxazolinyl derivatives.