Studies On The Chemical Constituents And Bioactivity Of Cryptocarya Brachythyrsa

Malignant tumors（cancers）are the second leading cause of death in the world by occupying about one-sixth of all deaths.World Health Organization（WHO）presented global cancer statistics 2018 showing there were about 18.1 million new cases and 9.6million deaths.Among them,the most commonly diagnosed and leading cause of cancer death is lung cancer,followed by female breast cancer,prostate cancer,colorectal cancer,stomach cancer,and liver cancer.Cancer statistics from China National Cancer Center（CNCC）in 2018 revealed 7 cancer diagnoses and 4 cancer deaths on each minute in China,cccupying about one-fifth and one-forth of all in the whole world,respectively,and the most common cancers are also lung cancer,stomach cancer,breast cancer,liver cancer,prostate cancer,and so on.Therefore,anticancer drugs play an important role for new drug discovery and development.Previous studies showed a series of secondary metabolites from genus Cryptocarya with strong cytotoxicity on human tumor cell lines.15 of 19 Cryptocarya species in China have never been studied before on their chemical constituents and bioactivity.Therefore,in this paper,Cryptocarya brachythyrsa,collected from Xishuangbanna,Yunnan Province,was selected for its chemical components study and preliminary anticancer activity evaluation.with a variety of separation materials and purification methods（MCI,CC,Sephadex gel,PHPLC）,41 compounds were isolated and their structures were elucidated on the base of extensive spectroscopic data analyses,including IR,UV,NMR,ESIMS,and ECD,especially 2D NMR techniques.Selected isolates were screened for their cytotoxic activity against a panel of human cancer cell lines and one human normal cell.This study aims to provide a theoretical basis for the exploitation of plants resources of Cryptocarya genus in China.The specific results are as follows:isolation,identification and evaluation for cytotoxity.41 compounds were isolated and identified from the 95%ethanol extract of C.brachythyrsa leaves and twigs,including 21 new compounds,which were classified as three newα-pyrones cryptobrachytones A?C（1?3）,three new chalcone derivatives crypbrachyones A?C（5?7）,eight new flavanone derivatives crypbrachythyrins A?H（10?17）,and seven newα-pyrone derivative?flavonoid complexes crypbrachyones D?H（30?34）and crypbrachythyrins I?J（35 and 36）.Furthermore,selected isolates 1?10,18?29,33 and 37?41 were evaluated for their cytotoxic activity against six human cancer cell lines A549（lung）,HCT-116（colon）,MDA-MB-231（breast cancer）,PC-3（prostate adenocarcinoma）,SH-SY5Y（neuroblastoma）,Hela（cervical cancer）and one human normal cell L02（liver）.The results revealed compounds 1,2,4?6,9,10,25?27and 33 showing significant activity with IC₅₀ values of 1.16-21.26μM.Amongst,compounds 1,2,4,10 and 25 inhibiting cancer cells with no effect on normal cell could be the lead compounds for anticancer drugs by further anticancer activity evaluation and action mechanism exploration.