title: Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids.
abstract: 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.
authors: Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano,via Venezian 21, 20133 Milan, Italy. luisella.verotta@unimi.it
authors: L
authors: L
authors: Verotta
authors: F
authors: F
authors: Orsini
authors: M
authors: M
authors: Sbacchi
authors: M A
authors: MA
authors: Scheildler
authors: T A
authors: TA
authors: Amador
authors: E
authors: E
authors: Elisabetsky
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000700:Analgesics; D011758:Pyrroles