Effect of glycodrugs in the chemotherapeutic response in pancreatic cancer.

GONZÁLEZ AL; WEIZ G; FERNANDEZ-ZAPICO ME,; MOLEJÓN MI; BRECCIA JD

Congreso; Reunion anual de sociedades de biociencias 2023; 2023

Drug glycosylation has emerged an alternative approach to improve pharmacokinetic properties, bioavailability and reduce the toxicity. Using as model pancreatic ductal adenocarcinoma (PDAC), the most common histological subtype of pancreatic cancer, we aimed at evaluating the anti-tumoral properties of glycosylated version of two polyphenolic chemotherapeutic agents (4-methylumbelliferone (4MU) and resorcinol (R) alone or in combination with standard cytotoxic therapy for PDAC. The enzymatic addition of the disaccharide rutinose using a diglycosidase was performed to obtain the respective glycodrugs named 4-methylumbelliferilrutinose (4MUR) and resorcinol-rutinoside (RR).Our experiments showed that the monotreatment with the glycodrugs did not affect significantly cell viability, however, the combination with gemcitabine, a commonly used chemotherapeutic agent, show a synergistic effect in PDAC cell models. In Panc-1 cells, 4MUR showed an antineoplastic effect decreasing the cell viability 44% (100 nM of Gemcitabine/ 50nM of 4-MUR, 48 h, p