Semisynthesis and biological activity of aminoacyl triesters of squamocin, an annonaceous acetogenin.
A number of aminoacyl triesters of squamocin 1, a cytotoxic acetogenin isolated from the seeds of Annona reticulata, have been synthesized in two to three steps from protected (l)-aminoacids and squamocin 1 using standard coupling/deprotection procedures. These semisynthetic analogs were tested on submitochondrial particles (SMP) for their complex I inhibitory activities, and against KB 3-1 cells in vitro. All triesters derivatives exhibited a complete extinction of activity at the enzymatic level, correlated to a reduced though modulated cytotoxicity in comparison with squamocin 1. This activity can apparently be considered as a function of the amphipathy of the analogs, the more amphiphilic ones being the more cytotoxic.
Duval
Romain A
RA
Laboratoire de Pharmacognosie (BioCIS, UMR 8076 CNRS), Faculté de Pharmacie, rue J.B. Clément, 92296 Châtenay-Malabry Cedex, France.
Duret
Philippe
P
Lewin
Guy
G
Peris
Eva
E
Hocquemiller
Reynald
R
D031041:Annona / Q000737:chemistry*; D002460:Cell Line; D004952:Esters; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013367:Submitochondrial Particles / Q000187:drug effects
D004952:Esters; D005663:Furans; D007783:Lactones; C059660:squamocin