1 Synthesis And Anti-tumor Activities Of Bcl-2 Protein Inhibitors 2 Efficient Synthesis Of Hydroxytyrosol

This thesis includes two sections.Apoptosis is essential for the normal growth of multicellular organisms, apoptosis dysregulation can cause a number of cancers. Bcl-2 family proteins play key roles in apoptototic pathway. It was reported that anti-apoptotic Bcl-2 proteins could be used as a promising molecular target for the design of an entirely new class of anticancer drugs. Based on the reported structure WL-276, thirty-three new compounds were designed and synthesized starting from L-phe via a series of reactions with the total yield of 45% ~ 55%. All compounds were characterizd by 1H NMR, 13C NMR, and HR-MS. Their in vitro anti-tumor activity against HL-60, MDA-MB-231, PC-3, DU-145 cell lines was screened using MTT assay. Among these compounds, 3g-1 and 3g-2 displayed superior pharmacological activity to WL-276. Their in vivo anti-tumor activity is under further investigation.In the second section, a new efficient chemical synthetic method was explored for hydroxytyrosol. It was reported that hydroxytyrosol had a variety of biological activities, such as anti-aging, enhancing skin elasticity, preventing lung cancer, breast cancer, uterine cancer and prostate cancer. Hydroxytyrosol was mainly obtained through olive oil extraction. The reported chemical synthesis of this compound either the starting material, or individual intermediates was very expensive. We reported herein an efficient and practical method for the chemical synthesis of hydroxytyrosol. The target compound was characterizd by 1H NMR, 13C NMR, and HR-MS.