Displaying publications 1 - 20 of 129 in total

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  1. Quinoline, Indole, and Isogranatanine Alkaloids from Malayan Leuconotis eugeniifolia
    Tan YS, Ng MP, Tan CH, Tang WK, Sim KS, Yong KT, et al.
    J Nat Prod, 2024 Feb 23;87(2):286-296.
    PMID: 38284153 DOI: 10.1021/acs.jnatprod.3c00960
    Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 μM, respectively.
    Matched MeSH terms: Indole Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
  2. Psychoactive properties of mitragynine (kratom)
    Jansen KL, Prast CJ
    J Psychoactive Drugs, 1988 Oct-Dec;20(4):455-7.
    PMID: 3072396
    Matched MeSH terms: Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
  3. Kratom (Mitragyna speciosa): worldwide issues
    Ramanathan S, McCurdy CR
    Curr Opin Psychiatry, 2020 07;33(4):312-318.
    PMID: 32452943 DOI: 10.1097/YCO.0000000000000621
    PURPOSE OF REVIEW: To inform readers about the increasingly popular Western dietary supplement, kratom (Mitragyna speciosa) and how the products are available in the Western world compared with traditional Southeast Asian use. Kratom has been traditionally used for increasing stamina of outdoor laborers (farmers), mood enhancement, pain, and opium addiction. Interestingly, kratom has been reported to have a paradoxical effect in that stimulant feelings, and sedative feelings can be obtained depending on the amount utilized. There are several biologically active alkaloids present in kratom.

    RECENT FINDINGS: Recent studies have been focused on the interactions of mitragynine, the most abundant alkaloid, and opioid-like effects. This has been driven by the harm that kratom products have produced in the Western world, in stark contrast to the lack of harm in Southeast Asian traditional use over centuries. Many users in the Western world ingest kratom for mood enhancement and/or to ween themselves from prescription or illicit opioids. Highly concentrated products and recreational use and misuse have resulted in individuals pushing doses to levels that have not been imagined or ever studied in animal, let alone humans.

    SUMMARY: Kratom, as a preparation and how it is utilized is different around the world.

    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
  4. Preparation and Preliminary Structure-Activity Relationship Studies of Schwarzinicine A Analogs as Vasorelaxant Agents
    Lee FK, Chan NJ, Krishnan P, Datu Abdul Salam DS, Chee XW, Muhamad A, et al.
    J Nat Prod, 2024 Apr 26;87(4):675-691.
    PMID: 38442031 DOI: 10.1021/acs.jnatprod.3c00707
    Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.
    Matched MeSH terms: Alkaloids/pharmacology
  5. A review on Mitragyna speciosa (Rubiaceae) as a prominent medicinal plant based on ethnobotany, phytochemistry and pharmacological activities
    Begum T, Arzmi MH, Khatib A, Uddin ABMH, Aisyah Abdullah M, Rullah K, et al.
    Nat Prod Res, 2025 Mar;39(6):1636-1652.
    PMID: 38923960 DOI: 10.1080/14786419.2024.2371564
    Mitragyna speciosa Korth (kratom) is a tropical indigenous tree of Southeast Asia. It is commonly consumed by the people due to its various pharmacological properties. The leaves of this plant are traditionally used for the treatment of several diseases including pain, fever, cough, anxiety, depression, obesity, diarrhoea, wound healing, diabetes, hypertension as well as for the prevention of cancer and improvement of sexual performance. Phytochemical investigations have confirmed the presence of more than forty alkaloids along with the presence of other bioactive secondary metabolites. Among the alkaloids isolated, mitragynine and 7-hydroxymitragynine along with their derivatives have been widely evaluated and reported to possess various pharmacological effects. Hence, the aim of this review is to shed light on the traditional uses of kratom and the scientific studies to justify the folkloric claims and active principles responsible for the various medicinal effects associated with the leaves of this plant. This review highlights the potential benefits and toxicities associated with M. speciosa leaves along with the phytochemistry. Moreover, the existing gaps in the field of M. speciosa study have been identified along with the future directions to further avail the benefits of this plant species.
    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology
  6. [Kratom-From natural remedy to addictive drug and back]
    Müller CP, Yang Y, Singh D, Lenz B, Müller E
    Nervenarzt, 2024 Sep;95(9):824-829.
    PMID: 39085520 DOI: 10.1007/s00115-024-01721-6
    BACKGROUND: Kratom/ketum is a psychoactive herbal preparation that has been used for a long time as a remedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used.

    OBJECTIVE: The current research on kratom and its ingredients is presented.

    MATERIAL AND METHODS: An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed.

    RESULTS: Consumption is accompanied by several instrumentalizeable effects so that kratom is used as a therapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7‑hydroxy-mitragynine are considered mainly responsible for the effect. Both have a complex pharmacology that involves partial µ‑opioid receptor agonism.

    DISCUSSION: Epidemiological, clinical and neurochemical studies have shown that kratom only has a limited addictive drug profile, which might suggest a medical use as a remedy or substitute in addiction treatment.

    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology
  7. Macroline-Sarpagine Bisindole Alkaloids with Antiproliferative Activity from Alstonia penangiana
    Yeap JS, Saad HM, Tan CH, Sim KS, Lim SH, Low YY, et al.
    J Nat Prod, 2019 11 22;82(11):3121-3132.
    PMID: 31642315 DOI: 10.1021/acs.jnatprod.9b00712
    A methanol extract of the stem bark of the Malayan Alstonia penangiana provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, 1-6) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, 7). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (1-6) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC50 values: 0.02-9.0 μM).
    Matched MeSH terms: Alkaloids/pharmacology*; Indole Alkaloids/pharmacology*
  8. Leuconoxine, kopsinitarine, kopsijasmine, and kopsinone derivatives from Kopsia
    Lim SH, Sim KM, Abdullah Z, Hiraku O, Hayashi M, Komiyama K, et al.
    J Nat Prod, 2007 Aug;70(8):1380-3.
    PMID: 17608533
    Four new indole alkaloids were obtained from two Kopsia species, 6-oxoleuconoxine (1) from the leaf extract of K. griffithii and kopsinitarine E (2), kopsijasminine (3), and kopsonoline (4) from the stem-bark extract of K. teoi. The structures of these alkaloids were determined using NMR and MS analysis. Kopsijasminine (3) showed moderate activity in reversing multidrug resistance in vincristine-resistant KB cells.
    Matched MeSH terms: Indole Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
  9. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa
    Takayama H
    Chem Pharm Bull (Tokyo), 2004 Aug;52(8):916-28.
    PMID: 15304982
    The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.
    Matched MeSH terms: Indole Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
  10. Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety
    Lim JL, Sim KS, Yong KT, Loong BJ, Ting KN, Lim SH, et al.
    Phytochemistry, 2015 Sep;117:317-24.
    PMID: 26125941 DOI: 10.1016/j.phytochem.2015.06.024
    Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.
    Matched MeSH terms: Alkaloids/pharmacology*; Indole Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
  11. From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction
    Hassan Z, Muzaimi M, Navaratnam V, Yusoff NH, Suhaimi FW, Vadivelu R, et al.
    Neurosci Biobehav Rev, 2013 Feb;37(2):138-51.
    PMID: 23206666 DOI: 10.1016/j.neubiorev.2012.11.012
    Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca²⁺ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
    Matched MeSH terms: Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
  12. Eucophylline, a Tetracyclic Vinylquinoline Alkaloid from Leuconotis eugenifolius
    Deguchi J, Shoji T, Nugroho AE, Hirasawa Y, Hosoya T, Shirota O, et al.
    J Nat Prod, 2010 Oct 22;73(10):1727-9.
    PMID: 20836516 DOI: 10.1021/np100458b
    Eucophylline (1), a new tetracyclic vinylquinoline alkaloid, was isolated from the bark of Leuconotis eugenifolius together with leucophyllidine (2). The structure and absolute configuration of 1 were elucidated on the basis of 2D NMR correlations and simulated CD analysis. Leucophyllidine (2) showed iNOS inhibitory activity and decreased the iNOS protein expression dose-dependently.
    Matched MeSH terms: Alkaloids/pharmacology; Indole Alkaloids/pharmacology
  13. The inhibitory effects of mitragynine on P-glycoprotein in vitro
    Rusli N, Amanah A, Kaur G, Adenan MI, Sulaiman SF, Wahab HA, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2019 04;392(4):481-496.
    PMID: 30604191 DOI: 10.1007/s00210-018-01605-y
    Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.
    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
  14. Conolodinines A-D, Aspidosperma- Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa
    Sim DS, Navanesan S, Sim KS, Gurusamy S, Lim SH, Low YY, et al.
    J Nat Prod, 2019 04 26;82(4):850-858.
    PMID: 30869890 DOI: 10.1021/acs.jnatprod.8b00919
    Examination of the EtOH extract of the leaves of the Malayan Tabernaemontana corymbosa resulted in the isolation of four new (1-4) and two known bisindole alkaloids (5, 6) of the Aspidosperma- Aspidosperma type. The structures of these alkaloids were determined based on analysis of the spectroscopic data (NMR and HRESIMS). X-ray diffraction analyses of the related bisindole alkaloids conophylline (5) and conophyllinine (6) established the absolute configurations. Treatment of the bisindole alkaloid conophylline (5) with benzeneselenic anhydride gave, in addition to the known bisindole polyervinine (7) previously isolated from another Malayan Tabernaemontana, another bisindole product, 8, an isolable tautomer of 7. X-ray diffraction analyses yielded the absolute configurations of both bisindoles and in addition showed that polyervinine (7) exists primarily as the neutral dione structure. The bisindoles (1-8) and the related conophylline-type bisindoles (9-13) showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, A549, HT-29, and HCT 116 cells, with IC50 values for the active compounds in the 0.01-5 μM range.
    Matched MeSH terms: Indole Alkaloids/pharmacology*
  15. A Cytotoxic Indole Characterized by Incorporation of a Unique Carbon-Nitrogen Skeleton and Two Pentacyclic Corynanthean Alkaloids Incorporating a Substituted Tetrahydrofuranone Ring from Kopsia arborea
    Wong SK, Wong SP, Sim KS, Lim SH, Low YY, Kam TS
    J Nat Prod, 2019 07 26;82(7):1902-1907.
    PMID: 31241923 DOI: 10.1021/acs.jnatprod.9b00255
    Three new alkaloids were isolated from the bark extract of the Malayan Kopsia arborea, viz., arbophyllidine (1), an unusual pentacyclic, monoterpenoid indole characterized by an absence of oxygen atoms and incorporating a new carbon-nitrogen skeleton, and arbophyllinines A (2) and B (3), two pentacyclic corynanthean alkaloids incorporating a hydroxyethyl-substituted tetrahydrofuranone ring. The structures of the alkaloids were deduced based on analysis of the MS and NMR data and confirmed by X-ray diffraction analyses. The absolute configuration of arbophyllidine (1) was established based on experimental and calculated ECD data, while that of arbophyllinine A was based on X-ray diffraction analysis (Cu Kα). A reasonable biosynthetic route to arbophyllidine (1) from a pericine precursor is presented. Arbophyllidine (1) showed pronounced in vitro growth inhibitory activity against the HT-29 human cancer cell line with IC50 6.2 μM.
    Matched MeSH terms: Indole Alkaloids/pharmacology
  16. Fulltext Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells
    Tay YL, Amanah A, Adenan MI, Wahab HA, Tan ML
    Sci Rep, 2019 12 24;9(1):19757.
    PMID: 31874991 DOI: 10.1038/s41598-019-56106-6
    Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
  17. New indole alkaloids from Alstonia macrophylla
    Kam TS, Choo YM
    J Nat Prod, 2004 Apr;67(4):547-52.
    PMID: 15104482
    Ten new indole alkaloids, alstomaline (1), 10,11-dimethoxynareline (2), alstohentine (3), alstomicine (4), 16-hydroxyalstonisine (5), 16-hydroxyalstonal (6), 16-hydroxy-N(4)-demethylalstophyllal oxindole (7), alstophyllal (8), 6-oxoalstophylline (9), and 6-oxoalstophyllal (10), in addition to 21 other known ones, were obtained from the leaf extract of the Malayan Alstonia macrophylla. The structures were determined using NMR and MS analysis.
    Matched MeSH terms: Indole Alkaloids/pharmacology
  18. Cardiovascular effects in the rat of dihydrocorynantheine isolated from Uncaria callophylla
    Chang P, Koh YK, Geh SL, Soepadmo E, Goh SH, Wong AK
    J Ethnopharmacol, 1989 Apr;25(2):213-5.
    PMID: 2747255
    Matched MeSH terms: Alkaloids/pharmacology*
  19. A new phytochemical survey of Malaysia. V. Preliminary screening and plant chemical studies
    Teo LE, Pachiaper G, Chan KC, Hadi HA, Weber JF, Deverre JR, et al.
    J Ethnopharmacol, 1990 Feb;28(1):63-101.
    PMID: 2314111
    A large phytochemical survey of the flora of the Malaysian Peninsula and Sabah is described, covering the systematic search for alkaloids, and partly, for saponins and flavonoids. Details of some chemical studies are reported. This emphasizes the great interest of such a study.
    Matched MeSH terms: Alkaloids/pharmacology
  20. Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids
    Kam TS, Subramaniam G, Sim KM, Yoganathan K, Koyano T, Toyoshima M, et al.
    Bioorg Med Chem Lett, 1998 Oct 06;8(19):2769-72.
    PMID: 9873619
    A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.
    Matched MeSH terms: Alkaloids/pharmacology*
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