Synthesis of a resveratrol analogue with high ceramide-mediated proapoptotic activity on human breast cancer cells.
Resveratrol, a natural product with a stilbene structure, exerts profound proapoptotic activity in human cancer cells, by triggering the accumulation of ceramide, a bioactive sphingolipid. We studied the biological effects of seven methoxylated and/or naphthalene-based resveratrol analogues and compared these compounds with resveratrol with the objective to identify an analogue with higher ceramide-mediated proapoptotic activity relative to resveratrol. Here we show that the compound with three hydroxyls and a naphthalene ring is the most effective in triggering apoptosis coupled to the induction of endogenous ceramide in human cancer cells.
Minutolo
Filippo
F
Department of Pharmaceutical Sciences, University of Pisa, via Bonanno 6, 56126 Pisa, Italy.
Sala
Giusy
G
Bagnacani
Annalisa
A
Bertini
Simone
S
Carboni
Isabella
I
Placanica
Giorgio
G
Prota
Giovanni
G
Rapposelli
Simona
S
Sacchi
Nicoletta
N
Macchia
Marco
M
Ghidoni
Riccardo
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002518:Ceramides / Q000096:biosynthesis*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002518:Ceramides; D013267:Stilbenes; D000077185:Resveratrol