65120-75-4Relevant academic research and scientific papers
Synthesis and antitumor activities of sinomenine derivatives on rings A and C
Wei, Can-Jing,Xu, Fang,Shi, Meng-Jiao,Hu, Jia-Wen,Wang, Jia-Jia,Zhen, Bo,Wang, Xue,Ji, Teng-Fei,Wang, Jin-Hua,Du, Guan-Hua
, p. 277 - 291 (2018)
A series of new sinomenine derivatives were designed, synthesized, and evaluated in tumor inhibitory activity, such as human triple negative breast cancer cell line (MDA-MB-231), glioma cell line (A172), human lung cancer cell line (A549), human colon cancer cell line (HCT-8). The modifications were carried out on rings A and C of the sinomenine by esterificating on phenolic hydroxyl with good yields. The highlight of this work was that the synthetic procedures were concise and sinomenine derivatives demonstrated promising antitumor activities.
Design, synthesis, and pharmacological evaluation of sinomenine derivatives on rings A and C: Novel compounds screening for aplastic anemia targeting on cytotoxic T lymphocyte
Zhang, Ziqian,Wang, Hongjian,Yuan, Jiqiao,Li, Xuyu,Fang, Nan,Lin, Mingbao,Hou, Qi,Ji, Tengfei
, (2021/08/27)
Cytotoxic T lymphocyte (CTL), a key effector cell in aplastic anemia (AA) immune injury, is shown to be a potential target for AA drug therapy. However, there is no candidate for this target till now. Oriented by the inhibition activity of CTL and macrophage derived nitric oxide (NO), a series of novel sinomenine derivatives on rings A and C are designed, synthesized and screened. Among them, compound 3a demonstrates the best inhibitory activity on CTL with an IC50 value of 2.3 μM, and a 97.1% inhibiton rate on macrophage NO production without significant cytotoxicity. Further, compound 3a exhibits substantial therapeutic efficacy on immune-mediated BM failure in AA model mice by improving the symptoms of anemia and the function of BM hematopoiesis, and shows more advantages in life quality improving than cyclosporine A (CsA). Its efficacy on AA at least partly comes from targeting on activated cluster of differentiation (CD)8+ T cell. Additionally, 3a also shows much less toxicity (LD50 > 10.0 g/kg) than sinomenine (LD50 = 1.1 g/kg) in preliminary acute toxicity assessment in mice, and has a low risk to inhibit hERG to cause cardiotoxicity. These results indicate that compound 3a merits further investigation for AA treatment by targeting on CTL.
