Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids.
Hodgkinsine, a trimeric pyrrolidinoindoline type alkaloid, present as a major constituent of Psychotria spp. (Rubiaceae), has shown to produce dose-dependent, naloxone reversible, analgesic effect in thermal models of nociception and in the capsaicin-induced pain. SAR studies have been initiated by synthesizing the three diastereomeric dimers (chimonanthines) (11-13) which were evaluated in vitro and in vivo along with the synthetic intermediates. Strong binding affinities for mu opioid receptors were found for (-)- and (+)-chimonanthine monourethanes (9 and 10), whereas (-)-, (+)- and (meso)-chimonanthine (11-13) and hodgkinsine displayed low affinity. In vivo data have shown that only (+)-chimonanthine (12) and calycosidine resemble the analgesic profile found for hodgkinsine.
Verotta
L
L
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano,via Venezian 21, 20133 Milan, Italy. luisella.verotta@unimi.it
Orsini
F
F
Sbacchi
M
M
Scheildler
M A
MA
Amador
T A
TA
Elisabetsky
E
E
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*
D000470:Alkaloids; D000700:Analgesics; D011758:Pyrroles