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 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.

Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids / L. Verotta, F. Orsini, M. Sbacchi, M. Scheildler, T. Amador, E. Elisabetsky. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 10:7(2002 Jul), pp. PII S0968-0896(02)00078-0.2133-PII S0968-0896(02)00078-0.2142.

Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids

L. Verotta
Primo
;
F. Orsini
Secondo
;
2002

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 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.
psychotria-colorata; enantioselective construction; high-affinity; receptor; dialkylation; binding
Settore CHIM/06 - Chimica Organica
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/177036
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