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Synthesis and interaction of sterol-uridine conjugate with DMPC liposomes studied by differential scanning calorimetry

Escobar, Jhon Fernando Berrío, Restrepo, Manuel Humberto Pastrana, Fernández, Diana Margarita Márquez, Martínez, Alejandro Martínez, Giordani, Cristiano, Castelli, Francesco, Sarpietro, Maria Grazia
Colloids and surfaces 2018 v.166 pp. 203-209
antineoplastic agents, cell membranes, colloids, differential scanning calorimetry, esterification, lipophilicity, models, phospholipids, uridine
Differential scanning calorimetry (DSC) is a thermoanalytical technique which provides information on the interaction between drugs and models of cell membranes. Studies on the calorimetric behavior of hydrated phospholipids within liposomes are employed to shed light on the changes in the physico-chemical properties when interacting with drugs. In this report, new potential anti-cancer drugs such as uridine and uridine derivatives (acetonide and its succinate), 3β-5α,8α-endoperoxide-cholestan-6-en-3-ol (5,8-epidioxicholesterol) and conjugate (uridine acetonide-epidioxicholesterol succinate) have been synthesized. Steglich esterification method using coupling agents allowed to obtain the uridine acetonide-sterol conjugate. The study on the interaction between the drugs and dimiristoyl-phophatidilcholine (DMPC) liposomes has been conducted by the use of DSC. The analysis of the DSC curves indicated that the uridine and derivatives (acetonide and its succinate) present a very soft interaction with the DMPC liposomes, whereas the 5,8-epidioxicholesterol and the conjugate showed a strong effect on the thermotropic behavior. Our results suggested that the lipophilic character of uridine acetonide-sterol conjugate improves the affinity with the DMPC liposomes.