Síntese e avaliação do potencial bioativo de derivados de chalconas

Abstract

The research and drug development consist of a long and complex process that begin with the search of new bioactive compounds. This work involved the synthesis, characterization and biological activity evaluation of compounds derivate from chalcones. Thirteen chalcones were obtained by Claisen-Schimdt aldolic condensation and two hidroxylated compounds by acid catalysis. All structures had their cytotoxicity evaluated against three human cancer cell lines of melanoma (MDA-MB-435), colon cancer (HCT-8) and central nervous system (SF-295). Out of the fifteen chalcones synthesized, the chalcones (E)-3-(3,4-dimethoxyphenyl)-1-phenyl-2-propen-1-one, (E)-3-(4-chlorophenyl)-1-phenyl-2-propen-1-one, (E)-3-(4-methoxyphenyl)-1-phenyl-2-propen-1-one e (E)-3-(4-nitrophenyl)-1-phenyl-2-propen-1-one showed relevant cytotoxic activity. The compound (E)-3-(4-nitrophenyl)-1-phenyl-2-propen-1-one showed high cytotoxic activity with IC50 less than 1 μg/mL with no selectivity in the tumor line cells. Evaluating the inhibition of enzymatic activity the best results were obtained against the cathepsin K, where the compounds (E)-3-(1,3-benzodioxol-5-il)-1-phenyl-2-propen-1-one, (E)-3-(4-fluorphenyl)-1-phenyl-2-propen-1-one, (E)-3-(4-chlorophenyl)-1-phenyl-2-propen-1-one e (E)-3-(4-methoxyphenyl)-1-phenyl-2-propen-1-one highlighted with inhibition exceeding 80% (125 μM). So, the promising chemical and biological results obtained here demonstrated the viability to achieve more active substances, which might represent new therapeutic possibilities.