2011 Fiscal Year Final Research Report

Drug discovery based on a new biological assay system using Yeast knock-out strain collection

Research Project

Project/Area Number	21580130
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Bioproduction chemistry/Bioorganic chemistry
Research Institution	Tokyo Denki University
Principal Investigator	KAWAI Satoru 東京電機大学, 理工学部, 教授 (10328528)
Project Period (FY)	2009 – 2011
Keywords	出芽酵母 / フラボノイド / クマリン / 合成化学
Research Abstract	Multidrug resistance(MDR) mediated by broad specificity transporters is one of the most important strategies used by pathogens, including cancer cells, to evade chemotherapy. In the yeast Saccharomyces cerevisiae, a complex pleiotropic drug resistance(PDR) network of genes involved in MDR is composed of the transcriptional regulators which activate expression of the ABC transporters-encoding genes. We have synthesized 154 flavonoids and screened for their antiproliferative activities toward isogenic S. cerevisiae strains deleted of PDR1, PDR3, PDR8, PDR10, PDR11, PDR16 and fluorinated flavonoids demonstrated the specific antiproliferative activity toward pdr1D strains. Our results may contribute to a better understanding of the mechanism of MDR. They also provide the indication of the physiological function of MDR transporters and suggest new approaches for cancer chemotherapy.