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

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2018-06, Vol.166, p.203-209
• Main Authors: Escobar, Jhon Fernando Berrío, Restrepo, Manuel Humberto Pastrana, Fernández, Diana Margarita Márquez, Martínez, Alejandro Martínez, Giordani, Cristiano, Castelli, Francesco, Sarpietro, Maria Grazia
• Format: Article
• Language: English
• Subjects: Calorimetry, Differential Scanning - methods; Dimyristoylphosphatidylcholine - chemistry; DSC; Liposome; Liposomes - chemistry; Prodrug; Prodrugs - chemistry; Sterols - chemistry; Uridine; Uridine - chemistry
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2018.03.023

[Display omitted] •Interaction of uridine and uridine derivatives with a biomembrane model was studied.•Differential scanning calorimetry was used.•The tested compounds affected the behavior of the biomembrane model.•The lipophilic derivatives exerted the strongest effect.•The lipophilic character of derivatives increased the affinity with biomembrane model. 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.