Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids.

ABSTRACT: Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.

SUBMITTER: Obeng S

PROVIDER: S-EPMC7676998 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids.

Obeng Samuel S Kamble Shyam H SH Reeves Morgan E ME Restrepo Luis F LF Patel Avi A Behnke Mira M Chear Nelson J-Y NJ Ramanathan Surash S Sharma Abhisheak A León Francisco F Hiranita Takato T Avery Bonnie A BA McMahon Lance R LR McCurdy Christopher R CR

Journal of medicinal chemistry 20191227 1

Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in <i>Mitragyna speciosa</i> (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid us ...[more]

PMID: 31834797

Similar Datasets

Evaluating kratom alkaloids using PHASE.

Project description:Kratom is a botanical substance that is marketed and promoted in the US for pharmaceutical opioid indications despite having no US Food and Drug Administration approved uses. Kratom contains over forty alkaloids including two partial agonists at the mu opioid receptor, mitragynine and 7-hydroxymitragynine, that have been subjected to the FDA's scientific and medical evaluation. However, pharmacological and toxicological data for the remaining alkaloids are limited. Therefore, we applied the Public Health Assessment via Structural Evaluation (PHASE) protocol to generate in silico binding profiles for 25 kratom alkaloids to facilitate the risk evaluation of kratom. PHASE demonstrates that kratom alkaloids share structural features with controlled opioids, indicates that several alkaloids bind to the opioid, adrenergic, and serotonin receptors, and suggests that mitragynine and 7-hydroxymitragynine are the strongest binders at the mu opioid receptor. Subsequently, the in silico binding profiles of a subset of the alkaloids were experimentally verified at the opioid, adrenergic, and serotonin receptors using radioligand binding assays. The verified binding profiles demonstrate the ability of PHASE to identify potential safety signals and provide a tool for prioritizing experimental evaluation of high-risk compounds.

| S-EPMC7053747 | biostudies-literature

The Chemistry of Kratom [<i>Mitragyna speciosa</i>]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids.

Project description:Two separate commercial products of kratom [Mitragyna speciosa (Korth.) Havil. Rubiaceae] were used to generate reference standards of its indole and oxindole alkaloids. While kratom has been studied for over a century, the characterization data in the literature for many of the alkaloids are either incomplete or inconsistent with modern standards. As such, full 1H and 13C NMR spectra, along with HRESIMS and ECD data, are reported for alkaloids 1-19. Of these, four new alkaloids (7, 11, 17, and 18) were characterized using 2D NMR data, and the absolute configurations of 7, 17, and 18 were established by comparison of experimental and calculated ECD spectra. The absolute configuration for the N(4)-oxide (11) was established by comparison of NMR and ECD spectra of its reduced product with those for compound 7. In total, 19 alkaloids were characterized, including the indole alkaloid mitragynine (1) and its diastereoisomers speciociliatine (2), speciogynine (3), and mitraciliatine (4); the indole alkaloid paynantheine (5) and its diastereoisomers isopaynantheine (6) and epiallo-isopaynantheine (7); the N(4)-oxides mitragynine-N(4)-oxide (8), speciociliatine-N(4)-oxide (9), isopaynantheine-N(4)-oxide (10), and epiallo-isopaynantheine-N(4)-oxide (11); the 9-hydroxylated oxindole alkaloids speciofoline (12), isorotundifoleine (13), and isospeciofoleine (14); and the 9-unsubstituted oxindoles corynoxine A (15), corynoxine B (16), 3-epirhynchophylline (17), 3-epicorynoxine B (18), and corynoxeine (19). With the ability to analyze the spectroscopic data of all of these compounds concomitantly, a decision tree was developed to differentiate these kratom alkaloids based on a few key chemical shifts in the 1H and/or 13C NMR spectra.

| S-EPMC7718854 | biostudies-literature

Monoterpenoid indole alkaloids from Alstonia rostrata

Project description:Four new monoterpenoid indole alkaloids, alstrostines C-F together with thirteen known alkaloids were isolated from the leaves and twigs of Alstonia rostrata. All structures of new compounds were elucidated based on NMR, FTIR, UV, and MS spectroscopic data. Alstrostines C-E might originate from keto-enol tautomerism of preakummicine during biogenetic pathway of akummicine. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-012-0019-y and is accessible for authorized users.

| S-EPMC4131594 | biostudies-literature

Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids.

Project description:In vitro cytochrome P450 inhibition of major kratom alkaloids: mitragynine (MTG), speciogynine (SPG), speciocilliatine (SPC), corynantheidine (COR), 7-hydroxymitragynine (7HMG) and paynantheine (PAY) was evaluated using human liver microsomes (HLMs) to understand their drug-drug interaction potential. CYP450 isoform-specific substrates of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4/5 were incubated in HLMs with or without alkaloids. Preliminary CYP450 inhibition (IC50) data were generated for each of these isoforms. In addition, the type of inhibition and estimation of the inhibition constants (Ki) of MTG and COR were determined. Among the tested alkaloids, MTG and COR were potent inhibitors of CYP2D6 (IC50, 2.2 and 4.2 μM, respectively). Both MTG and COR exhibited competitive inhibition of CYP2D6 activity and the Ki were found to be 1.1 and 2.8 μM, respectively. SPG and PAY showed moderate inhibition of CYP2D6 activity. Additionally, moderate inhibitory effects by SPC, MTG, and SPG were observed on CYP2C19 activity. Interestingly, inhibition of only midazolam hydroxylase CYP3A4/5 activity by COR, PAY, and MTG was observed while no inhibitory effect was observed when testosterone was used as a probe substrate. In conclusion, MTG and COR may lead to clinically significant adverse drug interactions upon coadministration of drugs that are substantially metabolized by CYP2D6.

| S-EPMC7902086 | biostudies-literature

Bioactive indole alkaloids isolated from Alstonia angustifolia.

Project description:Bioassay-guided fractionation was conducted on a CHCl3-soluble extract of the stem bark of Alstonia angustifolia (Apocynaceae) collected in Vietnam using the HT-29 human colon cancer cell line, and led to the isolation of a new sarpagine-type indole alkaloid (1), together with nine known alkaloids, including four macroline-derived alkaloids (2-5), a sarpagine-type alkaloid (6), and four macroline-pleiocarpamine bisindole alkaloids (7-10). The structure of the new compound (1) was determined on the basis of spectroscopic data interpretation. Compounds 1-10 were evaluated in vitro for their NF-?B (p65) inhibitory activity against the Hela cells in an ELISA assay. The new sarpagine alkaloid, N(4)-methyltalpinine (1), was found to show significant NF-?B inhibitory activity (ED50 = 1.2 µM). Furthermore, all the isolates (1-10) were evaluated in vitro for their antileishmanial activity, and compounds (1-4, 6 and 8-10) exhibited leishmaniacidal activity against promastigotes of Leishmania mexicana.

| S-EPMC4287998 | biostudies-literature

Three New Indole Alkaloids from Tabernaemontana divaricata.

Project description:Three new monoterpene indole alkaloids, 3?-hydroxymethyl-ibogamine (1), 3?-acetatemethoxyl-ibogamine (2), 16?-hydroxyl-ibogamine (3) together with six known alkaloids were isolated from the branches and leaves of Tabernaemontana divaricata (Apocynaceae). The structures of these alkaloids were determined by spectroscopic analyses. All isolated compounds showed no significant cytotoxicity against SGC-7901 gastric cancer, HeLa, and A-549 lung cancer cell lines (IC50 > 20 µM).

| S-EPMC5971036 | biostudies-literature

Three new indole alkaloids from Rauvolfia yunnanensis

Project description:One rare tetracyclic macroline-type indole alkaloid, named rauvoyunine A (1), and two new picraline-type alkaloids rauvoyunines B and C (2 and 3) were isolated from the aerial parts of Rauvolfia yunnanensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compounds 2 and 3 were evaluated for their in vitro cytotoxicity against five human tumor cell lines. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-011-0023-7 and is accessible for authorized users.

| S-EPMC4131643 | biostudies-literature

Four new indole alkaloids from Plantago asiatica

Project description:Graphical abstract Four new indole alkaloids, plasiaticines A-D (1–4), together with two known ones, were isolated from the seeds of Plantago asiatica. The structures of the new compounds were elucidated on the basis of comprehensive analysis of spectroscopic data. All compounds were tested for their cytotoxic activity, and all compounds except 4 were tested for their acetylcholinesterase (AChE) inhibitory activities. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-012-0082-4 and is accessible for authorized users.

| S-EPMC4131610 | biostudies-literature

Marine Indole Alkaloids-Isolation, Structure and Bioactivities.

Project description:Indole alkaloids are heterocyclic natural products with extensive pharmacological activities. As an important source of lead compounds, many clinical drugs have been derived from natural indole compounds. Marine indole alkaloids, from unique marine environments with high pressure, high salt and low temperature, exhibit structural diversity with various bioactivities, which attracts the attention of drug researchers. This article is a continuation of the previous two comprehensive reviews and covers the literature on marine indole alkaloids published from 2015 to 2021, with 472 new or structure-revised compounds categorized by sources into marine microorganisms, invertebrates, and plant-derived. The structures and bioactivities demonstrated in this article will benefit the synthesis and pharmacological activity study for marine indole alkaloids on their way to clinical drugs.

| S-EPMC8708922 | biostudies-literature

Indole Alkaloids from the Leaves of Nauclea officinalis.

Project description:Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.

| S-EPMC6273496 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data