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

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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.