Design, synthesis and evaluation of quercetin analogues and derivatives intended towards the treatment of prostate cancer.

摘要

In the United States, prostate cancer is the 2nd most common diagnosed form of cancer in men. Currently, the medical therapy for advanced, metastatic castration-resistant prostate cancer (mCRPC) is unmet.;Therefore we turn our attention towards natural products in search for possible answers. The current available in vitro researches as well as preliminary in vivo animal studies support the notion of quercetin as a potential anti-cancer agent. However, this potential cannot be appropriately reflected to the phase I clinical trial, probably due to quercetin's moderate potency and low bioavailability. In search of effective anti-prostate cancer agents using quercetin as a lead compound, our two approaches are i) to synthesize quercetin analogues with B-ring replaced with various basic Nitrogen-containing aromatic rings; and ii) to create a small library of alkylated derivatives of quercetin for exploration of structure-activity relationships. The structures of the synthesized and purified compounds have been elucidated based on extensive interpretation of their 1D and 2D NMR data, IR, and high resolution Mass. The in vitro anti-proliferative activity of the synthesized compounds have been evaluated using WST-1 cell proliferation assay towards androgen-dependent (LNCaP) and androgenindependent (PC-3, DU-145) prostate cancer cell lines.