Synthesis and antitumor activity of new d-seco and d-homo androstane derivatives

• Published in: Steroids Vol. 74; no. 12; pp. 983 - 988
• Main Authors: Djurendic, Evgenija A., Zavis, Marina P., Sakac, Marija N., Canadi, Janos J., Kojic, Vesna V., Bogdanovic, Gordana M., Gasi, Katarina M. Penov
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 04.11.2009; Elsevier
• Subjects: 16,17-Secosteroids; Androstane derivatives; Androstanes - chemical synthesis; Androstanes - chemistry; Androstanes - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biochemistry & Molecular Biology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; d-Homosteroids; Endocrinology & Metabolism; Fundamental and applied biological sciences. Psychology; Humans; In vitro cytotoxicity; Inhibitory Concentration 50; Life Sciences & Biomedicine; Science & Technology; Vertebrates: endocrinology; 16,17-Secosteroids; d-Homosteroids; In vitro cytotoxicity; Androstane derivatives; STEROIDS; BIOLOGICAL-ACTIVITY; D-Homosteroids; INHIBITORS; CANCER; Antineoplastic agent; Cytotoxicity; Biosynthesis; In vitro
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2009.07.007

Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile ( 1), the new 16,17-secoandrostane derivatives 4– 9 were synthesized. On the other hand, 3β-hydroxy-17-oxa- d-homoandrost-5-ene-16-one ( 10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER−, MDA-MB-231, prostate cancer AR−, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC 50 values being 2 μM and 0.55 μM, respectively. Compounds 6 (10 μM) and 14 (9 μM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1– 3, 5– 8, 10 and 12– 15 were not toxic to normal fetal lung fibroblasts cells, MRC-5.