Síntese e avaliação da atividade antioxidante e antitumoral de Chalconas

Abstract

Cancer is characterized by abnormal cell growth due to changes in the basic biological mechanisms that can spread to other organs. It is considered the second leading cause of death worldwide and its treatment consists of surgeries, radiotherapies, bone marrow transplantation and chemotherapies, which can be performed individually or together. Among the procedures, chemotherapy involves the use of antineoplastic drugs that act in the elimination of tumor cells. New molecules, such as chalcones, are being evaluated as prototypes for antineoplastic agents. Chalcones belong to flavonoids group, that can be obtained from natural sources or synthesized in the laboratory and have several pharmacological properties, such as antimicrobial, antitumor, anti-inflammatory and chemoprotective. The objective of this study was the synthesis and antioxidant and antitumor activity evaluation of chalcones. Thus, eleven (11) chalcones were synthesized by direct aldol condensation of Claisen-Schmidt with 80 to 99% yield and characterized by spectrophotometric methods (Gas Chromatography Mass Spectrometry - GC/MS, Infrared - IR and Nuclear Magnetic Resonance - NMR). After purity evaluation, the compounds were tested for antitumor activity by the Methyl Thiazole Tetrazolium test - MTT, antioxidant activity by sequestration of DPPH and Differential Pulse Voltammetry - DPV and conjugated addition to the double bond with N-Acetyl Cysteine - NAC. In antitumor activity, the compounds were tested on ovary adenocarcinoma (OVCAR-8), metastatic prostate (PC-3M), and bronchoalveolar lung (NCI-H358M) cells. Compound 7a was active for

all cells; 7c, 7i, 7j and 7k were active for the NCI-H358M lineage; 7b and 7g for PC- 3M; 7f and 7h for OVCAR-8 and NCI-H358M; 7d and 7e have IC50 values greater than

17 μM for all cells and were considered the most inactive. In the antioxidant activity by optical spectroscopy and EPR, it was possible to show that electron donor groups (hydroxyl, amino, methoxyls, for example) are directly related to the increase in activity and electron withdrawing groups (nitro, for example) with decreased of activity. Compounds 7g and 7j showed the highest uptake of the DPPH moiety. In the DPV compounds with the first peak of oxidation before 0.5V are classified as potential endogenous antioxidants, compounds 7g, 7j and 7k are potential endogenous antioxidants. Regarding the addition of NAC to the compounds, average binding percentage was 45% after 70 min of incubation. Thus, it is concluded that chalcones are promising molecules due their antitumor activity against the cell lines tested and antioxidant activity by both methods tested.