RESUMO
Breast cancer has the highest incidence and mortality in females, while prostate cancer has the second-highest incidence in males. Studies have shown that compounds from Brazilian green propolis have antitumor activities and can selectively inhibit the AKR1C3 enzyme, overexpressed in hormone-dependent prostate and breast tumors. Thus, in an attempt to develop new cytotoxic inhibitors against these cancers, three prenylated compounds, artepillin C, drupanin and baccharin, were isolated from green propolis to synthesize new derivatives via coupling reactions with different amino acids. All obtained derivatives were submitted to antiproliferative assays against four cancer cells (MCF-7, MDA MB-231, PC-3, and DU145) and two normal cell lines (MCF-10A and PNT-2) to evaluate their cytotoxicity. In general, the best activity was observed for compound6e, derived from drupanin, which exhibited half-maximal inhibitory concentration (IC50) of 9.6 ± 3 µM and selectivity index (SI) of 5.5 against MCF-7 cells.In silicostudies demonstrated that these derivatives present coherent docking interactions and binding modes against AKR1C3, which might represent a possible mechanism of inhibition in MCF-7 cells.
Assuntos
Aminoácidos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Cinamatos/farmacologia , Fenilpropionatos/farmacologia , Própole/química , Tricotecenos/farmacologia , Aminoácidos/análise , Aminoácidos/síntese química , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cinamatos/análise , Cinamatos/síntese química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fenilpropionatos/análise , Fenilpropionatos/síntese química , Própole/análise , Própole/síntese química , Própole/farmacologia , Relação Estrutura-Atividade , Tricotecenos/análise , Tricotecenos/síntese químicaRESUMO
In the present assay, the hepatoprotective activity of a sample of propolis from Rio Azul (PR) BRazil was studied using the model of acute hepatotoxicity induced by carbon tetrachloride (CCl4). The physical-chemical, chemical and toxicological profiles of the sample were also studied. The chemical analyses of the sample indicated the presence of gallic acid derivatives, 3-methoxy-4-hydroxy cinnamaldehyde as well as other unidentified compounds....
