homocastasterone and homobrassinolide

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)-3beta,22,23-trihydroxystigmast-5-ene and (22R,23R)-3beta,22,23-trihydroxystigmast-5-en-7-one, both comprising equatorial 3beta-hydroxyl group, exhibited the highest cytotoxicity, while the most polar 28-homobrassinolide and 28-homocastasterone, both comprising 2alpha,3alpha-dihydroxy groups, exhibited the lowest toxicity. Binding of (22R,23R)-22,23-dihydroxystigmastane derivatives to plasmatic membrane was suggested to be important for cytotoxicity.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cholestanones; Drug Screening Assays, Antitumor; Female; Humans; Male; Molecular Structure; Neoplasms; Stereoisomerism; Structure-Activity Relationship

Topics: Animals; Brain; Cholestanones; Cholestenones; Cockroaches; Dose-Response Relationship, Drug; Ecdysterone; In Vitro Techniques; Molecular Structure; Neurons