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https://open.uns.ac.rs/handle/123456789/18825
Назив: | Anticancer activity of novel steroidal 6-substituted 4-en-3-one D-seco dinitriles | Аутори: | Nikolić Andrea R. Kuzminac Ivana Z. Jovanović-Šanta Suzana S. Jakimov Dimitar Aleksić Lidija D. Sakač Marija |
Датум издавања: | 2018 | Часопис: | Steroids | Сажетак: | © 2018 Steroidal 16,17-seco-16,17a-dinitriles possessing 4-ene-3,6-dione (3), 6-methylene-4-en-3-one (5), (6E)-hydroxyimino-4-en-3β-ol (9) or (6E)-hydroxyimino-4-en-3-one (10) moiety were synthesized starting from 3β-acetoxy-16,17-secoandrost-4-ene-16,17a-dinitrile (1). Antiproliferative activity of the newly synthesized compounds, as well as previously synthesized 3-oxo-16,17-secoandrosta-1,4-diene-16,17a-dinitrile (VII), was tested in vitro. Compound 9 displayed submicromolar antiproliferative activity against human cervical carcinoma (HeLa) cells (IC500.48 μM), and compounds 3 and 10 expressed strong inhibitory potential against HeLa cells (IC504.31 μM and 2.64 μM, respectively). Also, compound 10 was effective in inhibiting estrogen hormone-independent (MDA-MB-231) cells (IC502.78 μM). All tested compounds had no influence on the proliferation of healthy cells (MRC-5). Since MDA-MB-231 breast cancer cells and HeLa cervical cancer cells were most sensitive to treatment by 16,17-seco-16,17a-dinitriles, apoptosis induction after treatment by compounds 3, VII, 9 and 10 was studied in these cells, to reveal the mechanism underlying cell growth inhibition. All tested compounds significantly induced apoptosis in both treated cell lines, which was evident from results obtained by a double AO-EB staining test and quantified by counting cells with apoptotic morphology after staining with Giemsa dye. Among all tested substances, (6E)-hydroxyimino-4-en-3-one derivative 10 expressed the most proapoptotic activity. | URI: | https://open.uns.ac.rs/handle/123456789/18825 | ISSN: | 0039-128X | DOI: | 10.1016/j.steroids.2018.03.009 |
Налази се у колекцијама: | PMF Publikacije/Publications |
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