Synthesis And Biological Activity Of New Curcumin And Artemisinin Derivatives

Numerous diverse bioactive natural products serve as a major source of modern drugs.This work aims to develop new curcumin and artemisinin derivatives,and to explore their biological activities.Curcumin is a polyphenol,extracted from the root block of Zingiberaceae and Araceae plants,exhibiting pharmacological effects of antioxidant,anti-inflammatory and anti-cancer.Curcumin is active against many cancers,including prostatic carcinoma,however,its mechanism of action still keeps unclear.Herein,we designed and completed the synthesis of a number of half molecules of curcumin and its variants.Inhibitory activity against human prostate cancer cells,proposed a possible active structural requirement of curcumin.Subsequently,we further synthesized 8 additional curcumin derivatives.Inhibitory activity revealed that derivatives 9c and 17a showed more potent activity than that of curcumin.The study of the anticancer mechanism of curcumin indicated that curcumin activates a novel kinase with a molecular weight of 30-67 KD,and inhibits the activity of YAP/TAZ protein,so as to fight cancer.Artemisinin is a colorless crystal,isolated from the leaves of Artemisia annua,showing effects of anti-malaria,anti-tumor,anti-fungal and immune regulation.Artemisinin derivatives are going to be synthesized for the treatment of leukemia in this work.We designed and synthesized 12 new artemisinin derivatives.Inhibitory activity against human acute myeloid leukemia cells revealed that all these artemisinin derivatives showed excellent activity.Among those,derivative 26b was found to exhibit the most potent activity.Subsequently,we also synthesized artemisinin derivatives 36,39a,44a and 47,and their biological activity has not been tested.