Synthesis and evaluation of anti-apoptotic activity of L-carnitine cyclic analogues and amino acid derivatives.
Two series of derivatives were synthesised. In one series (R)-4-hydroxy-2-pyrrolidinone was used as a mimic of cyclic L-carnitine analogue and in the second series 3-amino-2-piperidinone was used as a cyclic ornithine analogue. N-Benzyloxycarbonyl derivatives of some amino acids were also prepared. The newly synthesised compounds were tested for their ability to inhibit Fas-activated apoptosis of human Jurkatt T-cell line. The results confirm the previously described anti-apoptotic activity of carnitine and indicate new carnitine and amino acid analogues (1, 3, 6, 7, 20) that inhibit Fas-induced apoptosis.
Fringuelli
Renata
R
Department of Drug Chemistry and Technology, University of Perugia, Perugia, Italy. fringuel@unipg.it
Utrilla Navarro
M Pilar
MP
Milanese
Lara
L
Bruscoli
Stefano
S
Schiaffella
Fausto
F
Riccardi
Carlo
C
De Simone
Claudio
C
D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002331:Carnitine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D019169:Jurkat Cells
D000596:Amino Acids; D002331:Carnitine