Displaying publications 1 - 20 of 62 in total

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  1. 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/chemistry*
  2. Low YY, Gan CY, Kam TS
    J Nat Prod, 2014 Jun 27;77(6):1532-5.
    PMID: 24832351 DOI: 10.1021/np500289t
    Racemic andransinine (1), an indole alkaloid derivative obtained during isolation of alkaloids from Alstonia angustiloba and Kopsia pauciflora, was found to undergo spontaneous resolution when crystallized in EtOAc, forming racemic conglomerates (an equimolar mechanical mixture of enantiomerically pure individual crystals). X-ray analyses of the enantiomers (obtained from crystals from EtOAc solution and from chiral-phase HPLC) provided the absolute configuration of each enantiomer as (15R,16S,21R)-(+)-andransinine (1a or I+) and (15S,16R,21S)-(-)-andransinine (1b or I-).
    Matched MeSH terms: Indole Alkaloids/chemistry
  3. Ku WF, Tan SJ, Low YY, Komiyama K, Kam TS
    Phytochemistry, 2011 Dec;72(17):2212-8.
    PMID: 21889176 DOI: 10.1016/j.phytochem.2011.08.001
    A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.
    Matched MeSH terms: Indole Alkaloids/chemistry
  4. Tan CH, Sim DSY, Lim SH, Mohd Mohidin TB, Mohan G, Low YY, et al.
    Planta Med, 2022 Nov;88(14):1325-1340.
    PMID: 35100653 DOI: 10.1055/a-1755-5605
    Two iboga-vobasine bisindoles, 16'-decarbomethoxyvoacamine (1: ) and its 19,20-dihydro derivative, 16'-decarbomethoxydihydrovoacamine (2: ) from Tabernaemontana corymbosa exhibited potent cytotoxicity against the human colorectal adenocarcinoma HT-29 cells in our previous studies. Bisindoles 1: and 2: selectively inhibited the growth of HT-29 cells without significant cytotoxicity to normal human colon fibroblasts CCD-18Co. Treatment with bisindoles 1: and 2: suppressed the formation of HT-29 colonies via G0/G1 cell cycle arrest and induction of mitochondrial apoptosis. Owing to its higher antiproliferative activity, bisindole 2: was chosen for the subsequent studies. Bisindole 2: inhibited the formation of HT-29 spheroids (tumor-like cell aggregates) in 3D experiments in a dose-dependent manner, while an in vitro tubulin polymerization assay and molecular docking analysis showed that bisindole 2: is a microtubule-stabilizing agent which is predicted to bind at the β-tubulin subunit at the taxol-binding site. The binding resulted in the generation of ROS, which consequently activated the oxidative stress-related cell cycle arrest and apoptotic pathways, viz., JNK/p38, p21Cip1/Chk1, and p21Cip1/Rb/E2F, as shown by microarray profiling.
    Matched MeSH terms: Indole Alkaloids/chemistry
  5. Wong SP, Gan CY, Lim KH, Ting KN, Low YY, Kam TS
    Org. Lett., 2015 Jul 17;17(14):3628-31.
    PMID: 26183592 DOI: 10.1021/acs.orglett.5b01757
    A new monoterpene indole alkaloid characterized by an unprecedented pentacyclic cage skeleton, arboridinine (1), was isolated from a Malaysian Kopsia species. The structure and absolute configuration of the alkaloid were determined based on NMR, MS, and X-ray diffraction analysis. A possible biogenetic pathway from a pericine precursor is presented.
    Matched MeSH terms: Indole Alkaloids/chemistry
  6. Yap WS, Gan CY, Sim KS, Lim SH, Low YY, Kam TS
    J Nat Prod, 2016 Jan 22;79(1):230-9.
    PMID: 26717050 DOI: 10.1021/acs.jnatprod.5b00992
    Eleven new indole alkaloids (1-11) comprising seven aspidofractinine and four eburnane alkaloids, were isolated from the stem-bark extract of Kopsia pauciflora occurring in Malaysian Borneo. The aspidofractinine alkaloids include a ring-contracted, an additional ring-fused, a paucidactine regioisomer, two paucidactine, and one kopsine alkaloid. The structures of several of these alkaloids were also confirmed by X-ray diffraction analyses. The bisindole alkaloids isolated, norpleiomutine and kopsoffinol, showed in vitro growth inhibitory activity against human PC-3, HCT-116, MCF-7, and A549 cells and moderate effects in reversing multidrug-resistance in vincristine-resistant human KB cells.
    Matched MeSH terms: Indole Alkaloids/chemistry
  7. Gan CY, Low YY, Robinson WT, Komiyama K, Kam TS
    Phytochemistry, 2010 Aug;71(11-12):1365-70.
    PMID: 20542302 DOI: 10.1016/j.phytochem.2010.05.015
    Leucofoline and leuconoline, representing the first members of the aspidospermatan-aspidospermatan and eburnane-sarpagine subclasses of the bisindole alkaloids, respectively, were isolated from the Malayan Leuconotis griffithii. The structures of these bisindole alkaloids were established using NMR and MS analysis, and in the case of leuconoline, confirmed by X-ray diffraction analysis. Both alkaloids showed weak cytotoxicity towards human KB cells.
    Matched MeSH terms: Indole Alkaloids/chemistry
  8. Subramaniam G, Hiraku O, Hayashi M, Koyano T, Komiyama K, Kam TS
    J Nat Prod, 2008 Jan;71(1):53-7.
    PMID: 18078327
    Ten new indole alkaloids of the aspidofractinine type, in addition to several recently reported indole alkaloids and 20 other known alkaloids, were obtained from the leaf and stem-bark extract of the Malayan Kopsia singapurensis, viz., kopsimalines A-E (1-5), kopsinicine (6), kopsofinone (7), and kopsiloscines H-J (8-10). The structures of these alkaloids were determined using NMR and MS analysis. Kopsimalines A (1), B (2), C (3), D (4), and E (5) and kopsiloscine J (10) were found to reverse multidrug-resistance in vincristine-resistant KB cells, with 1 showing the highest potency.
    Matched MeSH terms: Indole Alkaloids/chemistry
  9. Kam TS, Pang HS, Choo YM, Komiyama K
    Chem Biodivers, 2004 Apr;1(4):646-56.
    PMID: 17191876
    Six new indole alkaloids, viz., (3S)-3-cyanocoronaridine (2), (3S)-3-cyanoisovoacangine (3), conolobine A (5), conolobine B (6), conolidine (7), and (3R/3S)-3-ethoxyvoacangine (8), in addition to 36 known ones, were obtained from the stem-bark extract of the Malayan Tabernaemontana divaricata. The structures were determined by NMR and MS analysis. The CN-substituted alkaloids showed appreciable cytotoxicity towards the KB human oral epidermoid carcinoma cell-line.
    Matched MeSH terms: Indole Alkaloids/chemistry
  10. Lim KH, Hiraku O, Komiyama K, Koyano T, Hayashi M, Kam TS
    J Nat Prod, 2007 Aug;70(8):1302-7.
    PMID: 17665953
    Nine new indole alkaloids, rhazinoline (1), 19(S)-methoxytubotaiwine (2), 19(R)-methoxytubotaiwine (3), kopsamidine A (4), kopsamidine B (5), kopsinidine A (6), kopsinidine B (7), paucidactine C (8), and pericine N-oxide (9), in addition to several recently reported novel indoles and 34 other known ones, were obtained from the stem-bark extract of the Malayan Kopsia arborea. The structures were determined using NMR and MS analysis. Valparicine (12) showed pronounced cytotoxic effects against KB and Jurkat cells (IC(50) 13.0 and 0.91 microM, respectively).
    Matched MeSH terms: Indole Alkaloids/chemistry
  11. Kam TS, Pang HS, Lim TM
    Org Biomol Chem, 2003 Apr 21;1(8):1292-7.
    PMID: 12929658
    The ethanol extract of the leaves of Tabernaemontana divaricata (double flower variety) provided a total of 23 alkaloids, including the new aspidosperma alkaloids, taberhanine, voafinine, N-methylvoafinine, voafinidine, voalenine and the new bisindole alkaloid, conophyllinine in addition to the previously known, biologically active bisindole, conophylline and its congener, conofoline. The structures of the new alkaloids were established by spectroscopic methods. The preparation and characterization of the corresponding quinones of the biologically active bisindoles are also described in relation to a structure-activity study of these compounds with respect to their action in stimulating insulin expression.
    Matched MeSH terms: Indole Alkaloids/chemistry*
  12. 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: Indole Alkaloids/chemistry*
  13. Chong KW, Yeap JS, Lim SH, Weber JF, Low YY, Kam TS
    J Nat Prod, 2017 11 22;80(11):3014-3024.
    PMID: 29087707 DOI: 10.1021/acs.jnatprod.7b00621
    Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K. pauciflora) found in two different geographical locations (Peninsular Malaysia and Malaysian Borneo) showed different patterns in the composition of the enantiomeric eburnane alkaloids. Revision of the absolute configurations of a number of new eburnane congeners (previously assigned based on the assumption of a common biogenetic origin to that of the known eburnane alkaloids co-occurring in the same plant) is required based on the present results.
    Matched MeSH terms: Indole Alkaloids/chemistry
  14. Kam TS, Tan SJ, Ng SW, Komiyama K
    Org. Lett., 2008 Sep 4;10(17):3749-52.
    PMID: 18683934 DOI: 10.1021/ol801354s
    A cytotoxic bisindole alkaloid possessing an unprecedented structure in which two indole moieties are bridged by an aromatic spacer unit has been isolated from Alstonia angustifolia. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway from pyrocatechuic acid and pleiocarpamine is presented.
    Matched MeSH terms: Indole Alkaloids/chemistry*
  15. Kam TS, Choo YM
    Alkaloids Chem Biol, 2006;63:181-337.
    PMID: 17133716
    Matched MeSH terms: Indole Alkaloids/chemistry*
  16. Wong CP, Seki A, Horiguchi K, Shoji T, Arai T, Nugroho AE, et al.
    J Nat Prod, 2015 Jul 24;78(7):1656-62.
    PMID: 26176165 DOI: 10.1021/acs.jnatprod.5b00258
    We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from Leuconotis griffithii, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annexin V and propidium iodide staining. Expression of all tested apoptosis-related proteins was also unaffected by Bis-A treatment. Bis-A was found to increase LC3 lipidation in MCF7 cells as well as A549 cells, suggesting that Bis-A cytostatic activity may be due to induction of autophagy. Subsequent investigation via Western blotting and immunofluorescence staining indicated that Bis-A induced formation but prevented degradation of autophagosomes. Mechanistic studies showed that Bis-A down-regulated phosphorylation of protein kinase B (AKT) and its downstream kinase, PRAS40, which is an mTOR repressor. Moreover, phosphorylation of p70S6K, an mTOR-dependent kinase, was also down-regulated. Down-regulation of these kinases suggests that the increase in LC3 lipidation may be due to mTOR deactivation. Thus, the cytostatic activity shown by Bis-A may be attributed to its induction of autophagosome formation. The Bis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway.
    Matched MeSH terms: Indole Alkaloids/chemistry
  17. Nugroho AE, Zhang W, Hirasawa Y, Tang Y, Wong CP, Kaneda T, et al.
    J Nat Prod, 2018 11 26;81(11):2600-2604.
    PMID: 30362746 DOI: 10.1021/acs.jnatprod.8b00749
    Three new bisindole alkaloids, bisleuconothines B-D (1-3), were isolated from the bark of Leuconotis griffithii. Their structures were elucidated by 1D and 2D NMR spectroscopy and DFT calculations. Bisleuconothine B (1) is the first monoterpene indole alkaloid dimer featuring bridges between both C-16-C-10' and C-2-O-C-9'. All compounds were deemed noncytotoxic (IC50 > 10 μM) when tested against A549 human lung adenocarcinoma cells.
    Matched MeSH terms: Indole Alkaloids/chemistry
  18. Nugroho AE, Hirasawa Y, Kawahara N, Goda Y, Awang K, Hadi AH, et al.
    J Nat Prod, 2009 Aug;72(8):1502-6.
    PMID: 19388660 DOI: 10.1021/np900115q
    A new bisindole alkaloid, bisnicalaterine A (1), consisting of two vobasine-type skeletons, and 3-epivobasinol (2) and 3-O-methylepivobasinol (3), with vobasine-type skeletons, were isolated from the leaves of Hunteria zeylanica, and their structures were elucidated on the basis of spectroscopic data and chemical correlation. Bisnicalaterine A showed moderate cytotoxicity against various human cancer cell lines.
    Matched MeSH terms: Indole Alkaloids/chemistry
  19. Hirasawa Y, Hara M, Nugroho AE, Sugai M, Zaima K, Kawahara N, et al.
    J Org Chem, 2010 Jun 18;75(12):4218-23.
    PMID: 20469917 DOI: 10.1021/jo1006762
    Two new bisindole alkaloids, bisnicalaterines B and C (1 and 2) consisting of an eburnane and a corynanthe type of skeletons, were isolated from the bark of Hunteria zeylanica. Their absolute structures were determined by combination of NMR, CD, and computational methods, and each of them was shown to be in an atropisomeric relationship. Bisnicalaterines B and C (1 and 2) showed potent vasorelaxant activity on isolated rat aorta.
    Matched MeSH terms: Indole Alkaloids/chemistry*
  20. Lee WT, Tan BK, Eng SA, Yuen GC, Chan KL, Sim YK, et al.
    Food Funct, 2019 Sep 01;10(9):5759-5767.
    PMID: 31453615 DOI: 10.1039/c9fo01357a
    A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity. Black sea cucumber (Holothuria atra) is a tropical sea cucumber species traditionally consumed as a remedy for many ailments. There is a paucity of knowledge on the anti-infective capacity of H. atra and the underlying mechanisms involved. The objective of this study is to utilize the Caenorhabditis elegans-P. aeruginosa infection model to elucidate the anti-infective properties of H. atra. A bioactive H. atra extract and subsequently its fraction were shown to have the capability of promoting the survival of C. elegans during a customarily lethal P. aeruginosa infection. The same entities also attenuate the production of elastase, protease, pyocyanin and biofilm in P. aeruginosa. The treatment of infected transgenic lys-7::GFP worms with this H. atra fraction restores the repressed expression of the defense enzyme lys-7, indicating an improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid, and inosine in this fraction. Collectively, our findings show that H. atra possesses anti-infective properties against P. aeruginosa infection, by inhibiting pathogen virulence and, eventually, reinstating host lys-7 expression.
    Matched MeSH terms: Indole Alkaloids/chemistry
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