Synthesis of amphiphilic resveratrol lipoconjugates and evaluation of their anticancer activity towards neuroblastoma SH-SY5Y cell line.
Resveratrol, a polyphenol present in grapes and other edible plants, possesses several important pharmacological activities, including anticancer activity. Nevertheless, its therapeutic use is still limited because of some unfavourable physicochemical and pharmacokinetic properties, mainly, poor cellular uptake and too rapid metabolism resulting in elimination from the body. To meet these drawbacks, some resveratrol conjugates would be useful, which would possess improved stability, uptake and bioavailability than the lead compound, and the ability to release it once it is internalized into the cell. In this paper we report a synthetic strategy which allowed us to obtain new amphiphilic resveratrol derivatives starting from different selectively protected resveratrol phosphoramidites or even from the resveratrol triphosphoramidite. Specifically, resveratrol was conjugated through phosphate bridge(s) to different lipophilic groups related to membrane lipids, such as cholesteryl or diacylglycero moieties. All the new lipoconjugates were tested towards human neuroblastoma SH-SY5Y cells and proved to be significantly more active than resveratrol, with a concentration-dependent activity.
Dipartimento di Scienze Chimiche, Università di Catania, V.le A. Doria 6, 95125 Catania, Italy.
Rosa
R
Chillemi
Dipartimento di Scienze Chimiche, Università di Catania, V.le A. Doria 6, 95125 Catania, Italy.
Nunzio
N
Cardullo
Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, V.le A. Doria 6, 95125 Catania, Italy.
Valentina
V
Greco
Dipartimento di Scienze del Farmaco, Università di Catania, V.le A. Doria 6, 95125 Catania, Italy.
Giuseppe
G
Malfa
Dipartimento di Scienze del Farmaco, Università di Catania, V.le A. Doria 6, 95125 Catania, Italy.
Barbara
B
Tomasello
Dipartimento di Scienze Chimiche, Università di Catania, V.le A. Doria 6, 95125 Catania, Italy. Electronic address: ssciuto@unict.it.
Sebastiano
S
Sciuto
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D015394:Molecular Structure; D009447:Neuroblastoma / Q000473:pathology*; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D013267:Stilbenes; D013501:Surface-Active Agents; D000077185:Resveratrol
Amphiphilic resveratrol lipoconjugates; Antitumour activity; Human fibroblasts; Neuroblastoma SH-SY5Y cells; Resveratrol