Chemical biology of MDR cancer selective cytotoxicity using natural product derivatives

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670054
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Kanazawa University
• Principal Investigator: Goto Kyoko 金沢大学, 薬学系, 准教授 (50180245)
• Co-Investigator(Renkei-kenkyūsha): TAMAI Ikumi 金沢大学, 医薬保健研究域薬学系, 教授 (20155237)
• Research Collaborator: GOTO Masuo University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Research Professor
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: フラボノイド / TEDB / 多剤耐性がん / Collateral sensitivity

Outline of Final Research Achievements

TEDB, a derivative of natural flavonoid desmosdumotin B, selectively inhibits multidrug resistant (MDR) tumor cell growth without any cytotoxicity against normal cells as well as non-MDR cells. Despite its unique antiproliferative activity, the mechanism of action is totally unclear. Using medicinal chemistry as well as chemical biological approaches of TEDB derivatives, we have discovered that TEDB with an artificial benzothiophene ring-B system induced a unique antimitotic bioactivity. The resulting antimitotic agent showed a wide spectrum against multiple cancer cell lines including MDR cells. Based on this finding, a series of new antimitotic flavonoids was designed and synthesized. We have also identified a cellular protein overexpressed in MDR cells as a novel candidate for overcoming MDR tumor using TEDB derivatives.

Free Research Field

創薬化学