Antiproliferative activity of steroidal oxime and its O-alkylated derivatives

Abstract

Oxime ethers have attracted much interest as important precursors and intermediates for the preparation of a wide variety of drugs and natural products. They can be easily converted into important functional groups such as amino alcohols and hydroxy ketones. Therefore, the development of methodologies for the preparation of oxime ethers is of considerable interest. Various researchers have studied the interesting biological properties of oxime ether derivatives such as anticonvulsant, anti-inflammatory, antineoplastic, anti-enteroviral, antimicrobial, antitumor, and anti-Helicobacter pylori activities [1]. Since clinical use of almost all anticancer drugs has been limited by the toxicity to normal tissues, important goal of cancer chemotherapy is to amplify the selective inhibition of tumor cells while decreasing toxicity to normal tissues. In order to develop more efficient and selective antitumor agents, here we report the efficient synthesis of 17-substituted O-alkylated androstane derivatives, and investigate their antiproliferative activity (IC50 after 72 h, MTT test) against three tumor cell lines (MDA-MB-231, HeLa and HT-29) and one healthy cell line (MRC-5). In continuation of our work on nitrogen containing androstane derivatives [2-4], synthesis of respective novel compounds and their evaluation in a human carcinoma cell lines will be presented and discussed. Acknowledgements: This work was financialy supported by Ministry of Education, Science and Technological development of the Republic of Serbia (Project No. 172021). [1] K. Sharma, S. B. Mishra, A. K. Mishra, Helv. Chim. Acta 94 (2011), 2256. [2] J. Ajdukovic, E. Djurendic, E. Petri, O. Klisuric, A. Celic, M. Sakac, D. Jakimov, K. Penov Gasi, Bioorg. Med. Chem. 21 (2013), 7257. [3] E. Djurendic, J. Ajdukovic, M. Sakac, J. Csanadi, V. Kojic, G. Bogdanovic, K. Penov Gasi, Eur. J. Med. Chem. 54 (2012), 784. [4] J. J. Ajdukovic, K. M. Penov Gasi, D. S. Jakimov, O. R. Klisuric, S. S. Jovanovic-Santa, M. N. Sakac, L. D. Aleksic, E. A. Djurendic, Bioorg. Med. Chem. 23 (2015), 1557.