Toxicity of (22R,23R)-22,23-dihydroxystigmastane derivatives to cultured cancer cells

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• 作者：Alex ; er Yu. Misharin ; Arif R. Mehtiev ; Vladimir N. Zhabinskii ; Vladimir A. Khripach ; Vladimir P. Timofeev ; Yaroslav V. Tkachev
• 关键词：Oxysterols ; Brassinosteroids ; Side chain conformation ; Cytotoxicity
• 刊名：Steroids
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：75
• 期：3
• 页码：287-294
• 全文大小：1149 K

文摘

Toxicity of eight 22,23-dihydroxystigmastane derivatives (four pairs of (22R,23R)- and (22S,23S)-isomers differing in steroid backbone structure) to human breast carcinoma MCF-7 cells was compared. For every pair of structurally related compounds, (22R,23R) isomer was found to be significantly more toxic than (22S,23S) isomer. Computational analysis showed that side chain of (22R,23R)-22,23-dihydroxystigmastane derivatives is rigid, whereas that of (22S,23S)-isomers is rather flexible. Structure of steroid backbone significantly affects cytotoxicity of (22R,23R)-22,23-dihydroxystigmastane derivatives to human breast carcinoma MCF-7 cells, human ovary carcinoma CaOv cells, and human prostate carcinoma LnCaP cells. (22R,23R)-3β,22,23-trihydroxystigmast-5-ene and (22R,23R)-3β,22,23-trihydroxystigmast-5-en-7-one, both comprising equatorial 3β-hydroxyl group, exhibited the highest cytotoxicity, while the most polar 28-homobrassinolide and 28-homocastasterone, both comprising 2α,3α-dihydroxy groups, exhibited the lowest toxicity. Binding of (22R,23R)-22,23-dihydroxystigmastane derivatives to plasmatic membrane was suggested to be important for cytotoxicity.