Chalcone derivatives synthesis and citotoxicity in hepatocellular carcinoma cells.

MARIEL MARDER; M. FERNANDA TRONCOSO; FABIOLA KAMECKI ; M. VICTORIA ESPELT

Congreso; Reunión Anual Sociedad Argentina de Fisiología, SAFIS; 2019

Hepatocellular carcinoma (HCC) is a lethal tumor that often occurs in patients with chronic liver disease and cirrosis. It has poor prognosis due to its high recurrence rate and resistance of chemotherapy. Lately several clinical investigations occurred in order to improve clinical outcome of HCC patients.Chalcones (1,3- diphenyl-2-propen-1-one) belong to the flavonoid family. They are composed by two aromatic rings joined by three carbon α,β-unsaturated carbonyl system. Natural and synthetic chalcone derivatives have shown promising biological activity as antioxidant, anti-inflammatory, anticancer, among others. Chalcone derivatives incubation of several cancer cell lines showed high cytotoxicity. So the aim of this work was to synthesize chalcones derivatives and analyze their citotoxicity in HCC cell lines.For chalcone synthesis, we used the reaction of each acetophenone and the corresponding benzaldehyde (aldol condensation) in the presence of NaOH. The synthesized chalcone derivatives were characterized using 1H nuclear magnetic resonance (1H-NMR), 13C-NMR and mass spectrometry (MS). HepG2 and Huh-7 cells viability was assessed using MTT assay.We synthesized the following chalcones: 2´-hydroxy-4´-methoxy-3-cholochalcone, 2´-hydroxy-4´-methoxy-4-chlorochalcone, 2´-hydroxy-3-nitrochalcone, 2´-hydroxy-6´-methoxychalcone; 2´-hydroxy-5´-methoxychalcone, 2´-hydroxy-4´-methoxychalcone, 2´-hydroxychalcone, chalcone, 2´-hydroxy-3-chlorochalcone. After 48 hs of incubation of 50 uM of each chalcone, cell viability was reduced between 35-60 % in both cell types. Cells were also incubated during 48 hs with 50 µM quercetin (a natural flavonoid) that have no effect on cell viability in HepG2 nor in Huh-7 cells. The IC50 for the most active derivative was 27.32 (20.14 to 37.07) µM for HepG2, and 23.81 (14.96 to 37.89) µM after 72 hs incubation. Our findings suggest that this new sythesized chalcones showed cytotoxic effects on HCC cells, and may be kept in mind for future cancer treatments. Future studies will focus on the relationship of each chalcone substitution and the effect on the type of cell death produced.