AUTHOR=Zhu Jun , Kong Ling-Qi , Chen Qin-Hua , Li Bin , Wu Lun , Ran Feng-Ying , Ke Li-Na , Zeng Xiao-Hua , Wang Hong-Mei 

TITLE=Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Rhopaladins’ Analog 4-Arylidene-5-Oxopyrrolidine Derivatives

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.898436

DOI=10.3389/fchem.2022.898436

ISSN=2296-2646

ABSTRACT=Marine alkaloids have novel structures and antitumor activities, therefore, we synthesized Rhopaladins’ analogues from marine alkaloids Rhopaladins A-D, and modified their structures to synthesize 4-benzylidene-5-pyrrolidone derivatives. Among the compounds, (2E，4E)-4-(4-chlorobenzylidene)-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) has high efficiency and less hepatotoxicity, with IC50 values of 4.66μM, 6.42μM, 17.66μM, 15.2μM, 12.36μM, 22.4μM，and 243.2μM in vitro anti-proliferative activity testing against cervical cancer C-33A, CaSki, SiHa and HeLa cells, human hepatocarcinoma HepG2 and 7402 cells, and human normal liver LO2 cell, respectively. Especially, the activity against human hepatocarcinoma cells was similar to that of Cisplatin, which was used as a positive control in this study. Next, the Annexin V/PI flow cytometry assay was used at different concentrations of RPDPRH to demonstrate that RPDPRH induced apoptosis of HepG2 and 7402 cells in a concentration-dependent manner. Finally, these results were further verified by Western blot analysis. In summary, the results of this study revealed that RPDPRH may be a potential anticancer compound play a significant role in the subsequent researches.