Síntese e avaliação biológica de derivados de bergenina e crisina como potenciais agentes antitumorais

Abstract

Polyphenols are compounds present in a variety of plant species and have a variety of reported biological activities. Bergenin and chrysin are naturally occurring polyphenol compounds with anti-inflammatory, antifungal, antidiabetic, neuroprotective, hepatoprotective, antioxidant and anticancer activities. Cancer is a disease that affects several populations around the world and new candidates for its treatment that are safe, low toxicity and selective are still being sought. In order to improve the bioavailability of bergenin and chrysin, for the purpose of performing antitumoral evaluation, functionalizations were performed on the skeleton of these polyphenols. The 1,2,3-triazole compounds of chrysin were synthesized with the application of CuAAC and, in addition, the study of the aminolysis of bergenin to obtain benzamides was carried out. However, the alkylation of phenolic hydroxyls and acylation of the glycosidic unit of bergenin were the most promising derivatives, with many of the synthesized compounds being new. Their cytotoxicity values were evaluated by the MTT assay in the inhibition of 4T1 cells (murine mammary adenocarcinoma), B16F10 (murine metastatic melanoma) and BHK21 (hamster kidney cells) in vitro. Promising results were obtained for compounds 3, 13, 14, which were more selective for metastatic melanoma, with compounds 13 and 14 showing a high selectivity index.