Antitumor effects of glycosylated 4-methylumbelliferone in a murine model of fibrosis associated- hepatocellular cancer

WEIZ, GISELA; MALVICINI MARIANA; RODRIGUEZ MARCELO; MAZZOLINI GUILLERMO; BRECCIA JAVIER D; MOLEJON, MARIA I

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Most of drugs lack of systems that direct them to the target tissues. In this way, a large part of drugs that remains in the bloodstream increases the secondaries effects in patients. The glycosylation of molecules is an interesting strategy for drug delivery to the specific target. The compound 4-methylumbelliferone (4MU) was described as inhibitor of the synthesis of hyaluronic acid and anticancer agent for hepatocellular carcinoma (HCC) associated with advanced fibrosis. In addition, treatment with 4MU remodel tumor microenvironment resulting in a potent inhibition of tumor growth. The aim of this work was to evaluate the antitumoral effect of the glycosylated 4MU.We modified 4MU, by the addition of a glycosidic moiety to obtain the product denominated4-methylumbelliferilrutinose (4MUR). Half maximal inhibitory concentration (IC50) of 4MU and 4MUR were determined on both, human and murine liver tumor cell lines (HUH 7 and Hepa 1.6, respectively) and compared the toxicity on normal human fibroblasts. The tumor cell lines were significantly more sensitive to the glycosylated compound 4MUR in a dose-dependent manner (p