| Project/Area Number |
15390004
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | University of Toyama (2005)
Toyama Medical and Pharmaceutical University (2003-2004) |
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Principal Investigator |
NEMOTO Hideo University of Toyama, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60006351)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYA Yuji University of Toyama, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (50255858)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | OSW-1 / antitumor activity / anticancer agent / steroid / structure-activity relationship / シスプラチン / オルトキノジメタン / ベンゾシクロブテン |
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| Research Abstract |
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.
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