? Chalcone derivative synthesis and cytotoxicity in hepatocellular carcinoma cells.

KAMECKI, F; MARDER M; TRONCOSO, MF; ESPELT, MV

Congreso; SAFIS; 2019

Hepatocellular carcinoma (HCC) is a lethal tumor that often occurs in patients with chronic liver disease and cirrhosis. 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- diaryl-2-propen-1-ones) 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 activities as antioxidant, anti-inflammatory, anticancer, among others. So the aim of this work was to synthesize new chalcone derivatives and analyze their cytotoxicity in HCC cell lines.For chalcone synthesis, we used the reaction of each acetophenone and the corresponding benzaldehyde (aldol condensation) in the presence of aqueous NaOH solution. 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: 3-chloro-2´-hydroxy-4´-methoxychalcone, 2´-hydroxy-4´-methoxy-4-chlorochalcone, 2´-hydroxy-3-nitrochalcone, 2´-hydroxy-6´-methoxychalcone; 2´-hydroxy-5´-methoxychalcone, 2´-hydroxy-4´-methoxychalcone, 2´-hydroxychalcone, 2´-hydroxy-3-chlorochalcone. After 48 h incubation with 50 µM of each chalcone, cell viability was reduced between 35-60 % (versus vehicle 100%) in both cell types. Cells were also incubated during 48 h with 50 µM quercetin, a natural flavonoid with antigrowth activities against several types of cancers, that has no effect on cell viability in HepG2 nor in Huh-7 cells. We also determined the 50% inhibitory concentration (IC50) for chalcone, the nucleous base of all derivative compounds, which was 27.32 (20.14 to 37.07)µM for HepG2, and 23.81 (14.96 to 37.89)µM after 72 h incubation.Our findings demonstrate that these new sythesized chalcones show cytotoxic effects on HCC cells. Future studies will focus on the relationship between the type of substituents on the chalcone core and the mechanism involved in HCC cell death.