Design and Synthesis of New Anticancer Agents Based on OSW-1 Having Potent Antitumor Activity as a Lead Compound

点击翻译按钮获取中文摘要

Based on a potent antitumor steroidal saponin OSW-1,design, synthesis, and biological evaluation of new candidate for a clinically useful anticancer agent were performed. For this purpose, novel OSW-1 analogues, which have a simplified steroidal sglycon, were designed, and A-aromatic type of aglycon was synthesized successfully starting from commercially available estrone. Dissacharide moiety found in natural OSW-1 was introduced to the A-aromatic aglycon, and the OSW-1 analogue thus obtained was subjected to the evaluation of antitumor activity. This revealed that the analogue exhibited notable activity with a comparable potency to cisplatin, clinically used anticancer agent. Several analogues having different disaccharide structure were also synthesized, and it was found that a fluoro-containing derivative showed significant antitumor activity. Based on these results, further simplified steroidal aglycon, namely A-nor B-aromatic aglycon, was designed. The synthesis was accomplished using successive pericyclic reactions via electrocyclic cleavage of benzocyclobutene derivatives as a key reaction with an excellent stereoselectivity. Installation of a disaccharide moiety to the A-nor B-aromatic aglycon is now under investigation, and a structure-activity relationship study of the OSW-1 analogues thus obtained are planned in future.