Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Science, Beijing Normal University, 19 XinjiekouWai Avenue, Beijing 100875, China.
Research Group Pharmaceutical Bioinformatics, Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, 79106 Freiburg im Breisgau, Germany.
Molecules. 2021 Jun 7;26(11):3466. doi: 10.3390/molecules26113466.
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 and C on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, H-NMR, C-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 , , , , , , and 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.
青藤碱是一种具有多种生物活性的吗啡烷生物碱。在许多研究中，其衍生物对不同的癌细胞系显示出显著的细胞毒性活性。在这项研究中，通过修饰青藤碱 A 环上的活性位置 C 和 C，设计并合成了两个系列的青藤碱衍生物。通过光谱（IR、H-NMR、C-NMR 和 HRMS）对 23 种化合物进行了表征。进一步采用 MTT 和 CCK8 法评价了它们对 MCF-7、Hela、HepG2、SW480 和 A549 五种癌细胞系和正常细胞系 Hek293 的细胞毒性活性。含氯化合物与青藤碱的核结构相比表现出显著的细胞毒性活性。此外，我们通过分子对接搜索了与癌症相关的核心靶标，并验证了它们与衍生物的相互作用。含氯化合物 、 、 、 、 、 和 对四个核心靶标 AKT1、EGFR、HARS 和 KARS 的抑制作用最好。分子对接结果与细胞毒性结果一致。总的来说，结果表明含氯衍生物可能是开发新型抗癌药物的有前途的先导化合物。
