Marine alkaloids have novel structures and antitumor activities. Therefore, we synthesized rhopaladins’ analogs 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 4.66, 6.42, 17.66, 15.2, 12.36, 22.4, and 243.2 μM 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 cells, respectively. In particular, RPDPRH has similar activity to cisplatin on human hepatocarcinoma cells, and cisplatin served as a positive control in our study. Next, the apoptosis of HepG2 and 7402 cells induced by RPDPRH at different concentrations was detected by Annexin V/PI flow cytometry. Moreover, the expression of apoptotic proteins was detected by Western blot analysis. Finally, the results showed that RPDPRH could induce apoptosis of hepatocarcinoma cells by regulating Bax and Bcl-2 expressions. In summary, our results indicate that RPDPRH has the potential to serve as an antitumor agent and plays a significant role in future studies.
Many marine alkaloids possess interesting structures and antitumor activities. Thus, we have synthesized (2 E,4 E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives of the marine alkaloids, rhopaladins A–D. The cytotoxicities of these derivatives against C-33A, CaSki, SiHa, HeLa, HepG2, and LO2 cells are evaluated by MTT assays. The results show that (2 E,4 E)-2-(4-chlorostyryl)-4-benzylidene- N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide significantly inhibits cancer cell proliferation, with IC50 values against C-33A, CaSki, SiHa, HeLa, and HepG2 cells of 5.56, 9.15, 12.5, 21.4, and 14.5 μM, respectively, and an IC50 value of 86.77 μM against the normal LO2 cell line.
Cervical cancer seriously threatens women’s health, it seriously harm the patient’s physical and mental health. The new derivative of Acanthus ilicifolius Linn alkaloid 2-benzoxazone was obtained from o-aminophenol, substituted benzaldehyde, trichloroacetic acid and isocyanate via a tandem Ugi 4CC/SN cyclization (N-cyclohexyl-2-(2-benzoxazolone-3-yl)-2-p-trifluoromethylphenylacetamide, BOABB), and the toxicity of the new compound to the cervical cancer C-33A cells was detected by CCK-8 assay, wound healing assay and apoptotic assay. The results exhibited that BOABB had obvious inhibitory effect on C-33A cells, and the calculated IC50 was 32.3 μM. Wound healing assay showed that BOABB could significantly inhibit cell migration (P<0.05). The apoptotic assay demonstrated that BOABB has induced apoptosis in C-33A cells (from 10.86% to 34.70%).
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