Exploring the Chemistry of Alkaloids from MalaysianMitragyna speciosa(Kratom) and the Role of Oxindoles on Human Opioid Receptors

Nelson Jeng Yeou Chear, Francisco León, Abhisheak Sharma, Siva Rama Raju Kanumuri, Grant Zwolinski, Khalil A. Abboud, Darshan Singh, Luis F. Restrepo, Avi Patel, Takato Hiranita, Surash Ramanathan, Aidan J. Hampson, Lance R Mcmahon, Christopher R. McCurdy

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

Ten indole and oxindole alkaloids (1-10) were isolated from the freshly collected leaves of MalaysianMitragyna speciosa(Kratom). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data analysis. The spectroscopic data of mitragynine oxindole B (4) are reported herein for the first time. The spatial configuration of mitragynine oxindole B (4) was confirmed by single-crystal X-ray diffraction. Simultaneous quantification of the isolated alkaloids in theM. speciosaleaf specimens collected from different locations in the northern region of Peninsular Malaysia was also performed using UPLC-MS/MS. The oxindole alkaloids (1-4) and the indole alkaloid (10) were assessed for binding affinity at opioid receptors. Corynoxine (1) showed high binding affinity to μ-opioid receptors with aKivalue of 16.4 nM. Further, corynoxine (1) was 1.8-fold more potent than morphine in rats subjected to a nociceptive hot plate assay. These findings have important implications for evaluating the combined effects of the minor oxindole alkaloids in the overall therapeutic activity ofM. speciosa.

Original languageEnglish (US)
Pages (from-to)1034-1043
Number of pages10
JournalJournal of Natural Products
Volume84
Issue number4
DOIs
StatePublished - Apr 23 2021
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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