Structurally Diverse Limonoids from Trichilia connaroides and Their Antitumor Activities  

作　　者：Ying Yan Dan Wang Fang-Jiao Zhou Yu-Han Zhao Xu-Jie Qin Yu Zhang Xiao Ding Xiao-Jiang Hao 

机构地区：[1]State Key Laboratory of Functions and Applications of Medicinal Plants & College of Pharmacy,Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Medical University,Guiyang,Guizhou 550014,China [2]School of Medicine and Health Management,Guizhou Medical University,Guiyang,Guizhou 550025,China [3]Key Laboratory of Phytochemistry and Natural Medicines,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming,Yunnan 650201,China

出　　处：《Chinese Journal of Chemistry》2024年第24期3567-3580,共14页中国化学(英文版)

基　　金：Financial support for this study was provided by National Natural Science Foundation of China(82360687);Guizhou Provincial Science and Technology Project(ZK[2022]393);Key Research and Development Project of Yunnan Province(202203AC100009,202003AD150012);Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(2022YKZY001).

摘　　要：Twelve new limonoids(1—12),named trichilitins A—L,were isolated from the leaves and twigs of Trichilia connaroides,together with ten known compounds(13—22).The structures were elucidated by extensive spectroscopic investigations,X-ray diffraction analyses,and ECD calculations.Compound 1,which belongs to a unique class of ring B-seco limonoid,has been identified as 6/7/6/5 tetracyclic due to a key Baeyer-Villiger oxidation.Compounds 2—7 were identified as ring intact limonoids,while compounds 8—10 were established as ring D-seco ones,and 11 and 12 were determined to be rearranged ones.All of the compounds were tested for cytotoxicity against three human tumor cell lines(HCT-116,NCl-H1975,and SH-SY5Y).Compounds 6,7,13,14,and 19 exhibited significant cytotoxic effects,especially 7 exhibited significant cytotoxic effects against HCT-116 with an IC_(50)value of 0.035μmol·L^(–1)and was more active than the positive control,doxorubicin with an IC_(50)value of 0.20μmol·L^(–1).Compound 7 effectively induced apoptosis of HCT-116,which was associated with S-phase cell cycle arrest.Furthermore,the Western blot analysis showed that compound 7 could induce cell cycle arrest by promoting the expression levels of p53 and p21.

关 键 词：Natural products LIMONOIDS MELIACEAE Structure elucidation Trichilia connaroides Antitumor activities p53 and p21 Structure-activity relationships Cancer treatment 

分 类 号：R73[医药卫生—肿瘤]