Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway

Molecules

Jia-Li Song¹  Qian-Qian Zhang¹  Hua Zhang¹  Yu-Ying Zhang¹  Cheng-Shi Jiang¹  Liang Zhang² 

[1] School of Biological Science and Technology, University of Jinan, Jinan 250022, China;The Key Laboratory of Animal Resistant Biology of Shandong College of Life Sciences, Shandong Normal University, Jinan 250014, China;

关键词: coumarin;    2-cyanoacryloyl;    antiproliferative activity;    apoptosis;    caspase;   

DOI  :  10.3390/molecules23081972

来源: DOAJ

【 摘 要 】

A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 μM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.

【 授权许可】

Unknown