Síntese e avaliação das atividades antioxidante e citotóxica de análogos da curcumina e heterociclos tiazólicos

Abstract

Substances with antioxidant properties have been extensively studied because of their therapeutic potential in the treatment and/or prevention of numerous types of diseases, including cancer. Curcumin is one of the most studied antioxidant compound. The antioxidant activity of hydrazino-thiazoles derivatives has also been studied. In this work, the synthesis of curcumin analogues and hydrazino-thiazole derivatives with potential antioxidant and cytotoxic activities was planned. The synthesis of curcumin analogues was performed by aldol condensation reaction between cyclohexanone or acetone and aliphatic or aromatic aldehydes. The thiazole derivatives were obtained by condensation of aldehydes or ketones and thiosemicarbazide, followed by reaction of corresponding thiosemicarbazone with 2bromoacetophenone. Compounds were assayed in vitro for antioxidant activity using the DPPH radical capture method, ABTS radical and iron reduction method FRAP and for cytotoxic activity against a panel of human tumor cell lines, including HL60 (acute myeloid leukemia), HCT (colorectal carcinoma), JURKAT (acute lymphoblastic leukemia), MCF7 and MDA (breast) and THP1 (monocytic leukemia). The cytotoxicity of the compounds using Vero cell line was also established as a model to evaluate toxicity on normal cell lines. In antioxidant assay (DPPH), thiazole derivatives 5a, 5e and 5g showed the best results with IC50 of 97.1; 95.4 and 60.4 uM, respectively, over the activity of curcumin (IC50 = 167.8 mM). In the cytotoxicity assay, two of curcumin analogues displayed results more promising: 1f (HL60 IC50 = 9.8 µM, JURKAT IC50 = 6.4 µM, MDA IC50 = 26 µM, THP1 IC50 = 7.3 µM and VERO IC50 > 100 µM) and 2b (HL60 IC50 = 3.2 µM, HCT IC50 = 2.7 µM, MCF7 IC50 = 6.4 µM, MDA IC50 = 18.9, THP1 IC50 = 11.7 µM and VERO CI50 = 49 µM). Besides, compound 1f showed no cytotoxic effect on normal cells (Vero cells), indicating a good selectivity.