Synthesis and in vitro cytotoxic activity of semisynthetic derivatives in the santonin series.
The synthesis of two new santonin derivatives namely 3-oxo-6 beta-H-11 beta-phenylselenoeudesm-1,4-dien-6,13-olide and 3-oxo-6 beta H-eudesm-1,4,11-trien-6,13-olide is reported along with the results of a series of santonins tested for activity against the growth of KB cells in vitro, a human epidermoid nasopharynx carcinoma. Select compounds were found to be active at concentrations lower than 5 X 10(-5) M. In particular, the compound 2 alpha-bromo-3 beta-hydroxy-6 beta H-eudesm-11-en-6,13-olide exhibits an extremely low ID50 value at 0.33 X 10(-6) M. Some relationships between chemical structure and cytotoxic activity are suggested, i.e. the alpha-methylene-gamma-lactone moiety appears to be necessary for cytotoxic activity toward KB cells growth in vitro by santonin derivatives.
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007624:KB Cells; D012500:Santonin / Q000138:chemical synthesis* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D012500:Santonin