Síntese e avaliação da atividade antiproliferativa de novos compostos planejados por hibridação molecular da Curcumina e do Resveratrol

Abstract

Cancer is a disease characterized by uncontrolled proliferation of cells that have the ability to invade surrounding tissues and form metastases. Chemotherapy is an important clinical approach in the treatment of cancer, but their effectiveness is limited due to low selectivity and the development of resistance by tumor cells. On the context, it is crucial the search for new substances, that can improve the therapeutic approaches to cancer treatment. The antitumor activity of curcumin (5), a natural compound derived from Curcuma longa, has been widely reported. Similarly, resveratrol (7), a polyphenol present in a variety of food sources, has been considered as a potential chemoprotective/chemotherapeutic agent. However, clinical application of such compounds has been limited due to low solubility and poor bioavailability. Thus, this work aimed at the synthesis, characterization and evaluation of the antiproliferative activity of eight different compounds (PQM-160-167), of which six contain structural domains of analogy with curcumin (5) and resveratrol (7); and two are analogs of curcumin (5). The proliferative potential of these compounds was evaluated on different cell lines derived from human tumors. The results showed that substances PQM-162 and PQM-163, which are hybrids of curcumin and resveratrol, were more effective in reducing the viability of MCF 7 cells (IC50 for PQM-162 = 40.49 ± 1.01 µM and PQM-163 = 19.09 ± 0.67 µM) and HT 144 (IC50 PQM-163 = 25.23 ± 2.93 µM), which are derived from breast cancer and melanoma, respectively. The effect of PQM-162 and PQM-163 on lines MCF 7 and HT144 was higher than that observed for curcumin (IC50 for MCF 7 = 47.32 ± 2.33 µM and HT 144 = 42.76 ± 3.79 µM). Furthermore, it was shown that the reduction in viability induced by PQM-162 substance in MCF 7 cell cultures was due, at least in part, its ability to block the cell cycle in G2/M stage. Additional studies should be conducted to assess the toxicity profile of these compounds on normal cells and the possible mechanism of action.