Natural Products for the Treatment of Pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2020 Sep 15

PMID 32930582

Citations 29

Authors

Soumen Chakraborty

Susruta Majumdar

Affiliations

Soon will be listed here.

Abstract

Pain remains a very pervasive problem throughout medicine. Classical pain management is achieved through the use of opiates belonging to the mu opioid receptor (MOR) class, which have significant side effects that hinder their utility. Pharmacologists have been trying to develop opioids devoid of side effects since the isolation of morphine from , more commonly known as opium by Sertürner in 1804. The natural products salvinorin A, mitragynine, and collybolide represent three nonmorphinan natural product-based targets, which are potent selective agonists of opioid receptors, and emerging next-generation analgesics. In this work, we review the phytochemistry and medicinal chemistry efforts on these templates and their effects on affinity, selectivity, analgesic actions, and a myriad of other opioid-receptor-related behavioral effects.

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References

Takayama H, Misawa K, Okada N, Ishikawa H, Kitajima M, Hatori Y . New procedure to mask the 2,3-pi bond of the indole nucleus and its application to the preparation of potent opioid receptor agonists with a Corynanthe skeleton. Org Lett. 2006; 8(25):5705-8. DOI: 10.1021/ol062173k. View

Lee D, Karnati V, He M, Liu-Chen L, Kondaveti L, Ma Z . Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues. Bioorg Med Chem Lett. 2005; 15(16):3744-7. DOI: 10.1016/j.bmcl.2005.05.048. View

Munro T, Rizzacasa M . Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A. J Nat Prod. 2003; 66(5):703-5. DOI: 10.1021/np0205699. View

Lamb K, Tidgewell K, Simpson D, Bohn L, Prisinzano T . Antinociceptive effects of herkinorin, a MOP receptor agonist derived from salvinorin A in the formalin test in rats: new concepts in mu opioid receptor pharmacology: from a symposium on new concepts in mu-opioid pharmacology. Drug Alcohol Depend. 2011; 121(3):181-8. PMC: 3288203. DOI: 10.1016/j.drugalcdep.2011.10.026. View

Obeng S, Kamble S, Reeves M, Restrepo L, Patel A, Behnke M . Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids. J Med Chem. 2019; 63(1):433-439. PMC: 7676998. DOI: 10.1021/acs.jmedchem.9b01465. View

Kivell B, Prisinzano T . Kappa opioids and the modulation of pain. Psychopharmacology (Berl). 2010; 210(2):109-19. DOI: 10.1007/s00213-010-1819-6. View

Tidgewell K, Harding W, Schmidt M, Holden K, Murry D, Prisinzano T . A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A. Bioorg Med Chem Lett. 2004; 14(20):5099-102. DOI: 10.1016/j.bmcl.2004.07.081. View

Nozawa M, Suka Y, Hoshi T, Suzuki T, Hagiwara H . Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. Org Lett. 2008; 10(7):1365-8. DOI: 10.1021/ol800101v. View

Lee D, Ma Z, Liu-Chen L, Wang Y, Chen Y, Carlezon Jr W . New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human kappa opioid receptors. Bioorg Med Chem. 2005; 13(19):5635-9. DOI: 10.1016/j.bmc.2005.05.054. View

10.

Kruegel A, Gassaway M, Kapoor A, Varadi A, Majumdar S, Filizola M . Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators. J Am Chem Soc. 2016; 138(21):6754-64. PMC: 5189718. DOI: 10.1021/jacs.6b00360. View

11.

Bikbulatov R, Yan F, Roth B, Zjawiony J . Convenient synthesis and in vitro pharmacological activity of 2-thioanalogs of salvinorins A and B. Bioorg Med Chem Lett. 2007; 17(8):2229-32. PMC: 1905843. DOI: 10.1016/j.bmcl.2007.01.100. View

12.

Lee D, He M, Liu-Chen L, Wang Y, Li J, Xu W . Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A analogues. Bioorg Med Chem Lett. 2006; 16(21):5498-502. DOI: 10.1016/j.bmcl.2006.08.051. View

13.

Zjawiony J, Machado A, Menegatti R, Ghedini P, Costa E, Pedrino G . Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs. Front Psychiatry. 2019; 10:157. PMC: 6445891. DOI: 10.3389/fpsyt.2019.00157. View

14.

Ma J, Yin W, Zhou H, Liao X, Cook J . General approach to the total synthesis of 9-methoxy-substituted indole alkaloids: synthesis of mitragynine, as well as 9-methoxygeissoschizol and 9-methoxy-N(b)-methylgeissoschizol. J Org Chem. 2008; 74(1):264-73. PMC: 2654583. DOI: 10.1021/jo801839t. View

15.

Newman D, Cragg G . Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod. 2016; 79(3):629-61. DOI: 10.1021/acs.jnatprod.5b01055. View

16.

Roach J, Sasano Y, Schmid C, Zaidi S, Katritch V, Stevens R . Dynamic Strategic Bond Analysis Yields a Ten-Step Synthesis of 20-nor-Salvinorin A, a Potent κ-OR Agonist. ACS Cent Sci. 2018; 3(12):1329-1336. PMC: 5746855. DOI: 10.1021/acscentsci.7b00488. View

17.

Ma Z, Lee D . Revised structure of deacetyl-1,10-didehydrosalvinorin G. Tetrahedron Lett. 2008; 48(31):5461-5464. PMC: 2390872. DOI: 10.1016/j.tetlet.2007.05.179. View

18.

Riley A, Groer C, Young D, Ewald A, Kivell B, Prisinzano T . Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. J Med Chem. 2014; 57(24):10464-75. PMC: 4281103. DOI: 10.1021/jm501521d. View

19.

Stoeber M, Jullie D, Li J, Chakraborty S, Majumdar S, Lambert N . Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells. Elife. 2020; 9. PMC: 7041944. DOI: 10.7554/eLife.54208. View

20.

Burns A, Forsyth C . Intramolecular Diels-Alder/Tsuji allylation assembly of the functionalized trans-decalin of salvinorin A. Org Lett. 2007; 10(1):97-100. DOI: 10.1021/ol7024058. View