文献类型：期刊文献

英文题名：Design, Synthesis, Biological Evaluation and Silico Prediction of Novel Sinomenine Derivatives

作者：Li, Shoujie[1];Gao, Mingjie[2];Nian, Xin[3];Zhang, Liyu[4];Li, Jinjie[5];Cui, Dongmei[3];Zhang, Chen[4];Zhao, Changqi[1]

第一作者：Li, Shoujie

通讯作者：Zhao, CQ[1];Cui, DM[2];Zhang, C[3]

机构：[1]Beijing Normal Univ, Coll Life Sci, Beijing Key Lab, Gene Engn & Biotechnol, 19 XinjiekouWai Ave, Beijing 100875, Peoples R China;[2]Albert Ludwigs Univ Freiburg, Inst Pharmaceut Sci, Res Grp Pharmaceut Bioinformat, D-79106 Freiburg, Germany;[3]Zhejiang Univ Technol, Coll Pharmaceut Sci, 18 Chaowang Rd, Hangzhou 310014, Peoples R China;[4]Zhejiang Univ, Coll Pharmaceut Sci, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China;[5]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, 197 Beitucheng West Rd, Beijing 100191, Peoples R China

第一机构：Beijing Normal Univ, Coll Life Sci, Beijing Key Lab, Gene Engn & Biotechnol, 19 XinjiekouWai Ave, Beijing 100875, Peoples R China

通讯机构：[1]corresponding author), Beijing Normal Univ, Coll Life Sci, Beijing Key Lab, Gene Engn & Biotechnol, 19 XinjiekouWai Ave, Beijing 100875, Peoples R China;[2]corresponding author), Zhejiang Univ Technol, Coll Pharmaceut Sci, 18 Chaowang Rd, Hangzhou 310014, Peoples R China;[3]corresponding author), Zhejiang Univ, Coll Pharmaceut Sci, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China.

年份：2021

卷号：26

期号：11

外文期刊名：MOLECULES

收录：;Scopus(收录号：2-s2.0-85108218353);WOS:【SCI-EXPANDED(收录号:WOS:000660393000001)】；

语种：英文

外文关键词：sinomenine; synthesis; cancer; cytotoxic activity; docking study

摘要：Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C-1 and C-4 on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, H-1-NMR, C-13-NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF-7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine-containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer-related core targets and verified their interaction with derivatives through molecular docking. The chlorine-containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine-containing derivatives might be a promising lead for the development of new anticancer agents.