Hodgkinsine

drugbox
IUPAC_name = (3aR,8bR)-5,8b-bis [(3aR,8bR)-3-methyl-1,2,3a,4-tetrahydropyrrolo [2,3-b] indol-8b-yl] -3-methyl-1,2,3a,4-tetrahydropyrrolo [2,3-b] indole


width = 200
CAS_number = 18210-71-4
synonyms = Hodgkinsine
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PubChem = 442105
smiles = CN1CC [C@] 2( [C@@H] 1NC3=CC=CC=C32)C4=C5C(=CC=C4) [C@] 6(CCN( [C@H] 6N5)C) [C@@] 78CCN( [C@@H] 7NC9=CC=CC=C89)C
DrugBank =
C = 33 | H = 38 | N = 6
molecular_weight = 518.695 g/mol
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Hodgkinsine is an alkaloid found in plants of the "Psychotria" genus, particularly "Psychotria colorata", [Verotta L, Pilati T, Tatò M, Elisabetsky E, Amador TA, Nunes DS. Pyrrolidinoindoline Alkaloids from Psychotria colorata. "Journal of Natural Products". 1998 Mar 27;61(3):392-6. PMID 9548883] although it is also found in "Psychotria lyciiflora" [Jannic V, Guéritte F, Laprévote O, Serani L, Martin MT, Sévenet T, Potier P. Pyrrolidinoindoline alkaloids from Psychotria oleoides and Psychotria lyciiflora. "Journal of Natural Products". 1999 Jun;62(6):838-43. PMID 10395499] and probably other species in this family, [Elisabetsky E, Amador TA, Leal MB, Nunes DS, Carvalho ACT, Verotta L. Merging ethnopharmacology with chemotaxonomy: an approach to unveil bioactive natural products. The case of "Psychotria" alkaloids as potential analgesics. "Ciência e Cultura" 1997; 49:378-385.] as well as in the related species "Calycodendron milnei". [Saad HE, el-Sharkawy SH, Shier WT. Biological activities of pyrrolidinoindoline alkaloids from Calycodendron milnei. "Planta Medica". 1995 Aug;61(4):313-6. PMID 7480176]

Hodgkinsine has antiviral, antibacterial and antifungal effects, but has mainly been researched for the analgesic effects that it produces, and is thought to be one of the components responsible for the analgesic effects seen when "Psychotria colorata" is used in traditional medical practice in humans. It has been found to act as both a mu opioid agonist and an NMDA antagonist, [Amador TA, Verotta L, Nunes DS, Elisabetsky E. Antinociceptive profile of hodgkinsine. "Planta Medica". 2000 Dec;66(8):770-2. PMID 11199142] both of which are mechanisms of action shared with commonly used painkillers (morphine and ketamine respectively).

Hodgkinsine is a trimer composed of three pyrrolidinoindoline subunits, with the monomer closely resembling another alkaloid eseroline which has similar bioactivity. Due to its complex structure and multiple chiral centres, hodgkinsine has many stereoisomers and significant research has been undertaken to elucidate the structure-activity relationships of the various isomers and synthetic derivatives structurally derived from hodgkinsine. [Verotta L, Orsini F, Sbacchi M, Scheildler MA, Amador TA, Elisabetsky E. Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids. "Bioorganic and Medicinal Chemistry". 2002 Jul;10(7):2133-42. PMID 11983509] [Kodanko JJ, Overman LE. Enantioselective total syntheses of the cyclotryptamine alkaloids hodgkinsine and hodgkinsine B. "Angewandte Chemie (International Edition in English)". 2003 Jun 6;42(22):2528-31. PMID 12800178] [Kodanko JJ, Hiebert S, Peterson EA, Sung L, Overman LE, de Moura Linck V, Goerck GC, Amador TA, Leal MB, Elisabetsky E. Synthesis of all low-energy stereoisomers of the tris(pyrrolidinoindoline) alkaloid hodgkinsine and preliminary assessment of their antinociceptive activity. "Journal of Organic Chemistry". 2007 Oct 12;72(21):7909-14. PMID 17887704]

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