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Toh-seok Kam - One of the best experts on this subject based on the ideXlab platform.
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Conolodinines A–D, Aspidosperma–Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa
2019Co-Authors: Dawn Su-yin Sim, Yun-yee Low, Kae-shin Sim, Siew-huah Lim, Suerialoasan Navanesan, Subramaniam Gurusamy, Toh-seok KamAbstract: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
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Ajmaline, Oxindole, and Cytotoxic Macroline–Akuammiline Bisindole Alkaloids from Alstonia penangiana
2018Co-Authors: Joanne Soon-yee Yeap, Yun-yee Low, Siew-huah Lim, Kienthai Yong, Suerialoasan Navanesan, Subramaniam Gurusamy, Toh-seok KamAbstract:Examination of the EtOH extract of the Malayan Alstonia penangiana resulted in the isolation of 10 new Alkaloids, comprising two ajmaline (1, 2), four macroline oxindole (3–6), and four macroline–akuammiline Bisindole Alkaloids (7–10). The structures of these Alkaloids were determined based on analysis of the spectroscopic data and, in the case of the oxindole 6 and the Bisindole Alkaloid 7, also confirmed by X-ray diffraction analysis. The Bisindole Alkaloids 7 and 8 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, HT-29, HCT 116, and A549 cells with IC50 values in the 0.3–8.3 μM range
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Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C‑20α Substitution
2016Co-Authors: Choy-eng Nge, Kamweng Chong, Yun-yee Low, Noel F. Thomas, Siew-huah Lim, Toh-seok KamAbstract:Ten new indole Alkaloids (1–10) comprising five ibogan, two aspidosperman, one vincamine, and two Bisindole Alkaloids, in addition to 32 known Alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these Alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga Alkaloids, conodusines B (2) and C (3), and the iboga-containing Bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga Alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (−)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (−)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (−)-coronaridine. The configuration at C-20′ of the previously reported Tabernaemontana Bisindole Alkaloid 19′-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the Bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells
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Cytotoxic Vobasine, Tacaman, and Corynanthe-Tryptamine Bisindole Alkaloids from Tabernaemontana and Structure Revision of Tronoharine
2014Co-Authors: Dawn Su-yin Sim, Kamweng Chong, Choy-eng Nge, Yun-yee Low, Kae-shin Sim, Toh-seok KamAbstract:Seven new indole Alkaloids (1–7) comprising four vobasine, two tacaman, and one corynanthe-tryptamine Bisindole Alkaloid were isolated from the stem-bark extract of a Malayan Tabernaemontana. Two of the new vobasine Alkaloids (1, 3), as well as 16-epivobasine (15) and 16-epivobasenal (17), showed appreciable cytotoxicity toward KB cells (IC50 ca. 5 μg/mL). The structure of the known Tabernaemontana Alkaloid tronoharine (8) was revised based on newly acquired NMR data, as well as X-ray diffraction analysis
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angustilobine and andranginine type indole Alkaloids and an uleine secovallesamine Bisindole Alkaloid from alstonia angustiloba
Phytochemistry, 2011Co-Authors: Shin-jowl Tan, Yun-yee Low, Kanki Komiyama, Toh-seok KamAbstract: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.
James M Cook - One of the best experts on this subject based on the ideXlab platform.
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the enantiospecific stereospecific total synthesis of the ring a oxygenated sarpagine indole Alkaloids majvinine 10 methoxyaffinisine and na methylsarpagine as well as the total synthesis of the alstonia Bisindole Alkaloid macralstonidine
Journal of Organic Chemistry, 2003Co-Authors: Shuo Zhao, Xuebin Liao, Tao Wang, Judith L Flippenanderson, James M CookAbstract:The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated sarpagine indole Alkaloids (+)-Na-methylsarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia Bisindole Alkaloid macralstonidine (9), has been accomplished. This approach employed the Schollkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet−Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd0 coupling process and the asymmetric Pictet−Spengler reaction can be employed to synthesize both macroline (2) and Na-methylsarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole Alkaloids should find wide application for the synthesis of other Alkaloids for it is stereospecific and either enantiomer can be prepared with ease.
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enantiospecific total synthesis of anhydromacrosalhine methine and partial synthesis of the antiamoebic Bisindole Alkaloid macrocarpamine1
Journal of Organic Chemistry, 1998Co-Authors: Tong Gan, James M CookAbstract:An enantiospecific total synthesis of (−)-anhydromacrosalhine-methine (7a) was completed from d-(+)-tryptophan via the asymmetric Pictet−Spengler reaction. In addition, a partial synthesis of (−)-anhydromacrosalhine-methine (7a) was carried out from the natural product (+)-ajmaline (10). The coupling reaction of plant-derived (+)-pleiocarpamine (8) with synthetic diene 7a provided the antiamoebic Bisindole Alkaloid (−)-macrocarpamine (1) in 75% yield. This sequence serves as the first example of the action of a nucleophile at [at C(2)] on a protonated form [C(3)] of pleiocarpamine 8 in the Alstonia series to provide a Bisindole Alkaloid.
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partial synthesis of the antiamoebic Bisindole Alkaloid macrocarpamine
Tetrahedron Letters, 1996Co-Authors: Tong Gan, James M CookAbstract:Abstract The partial synthesis of the antiamoebic Bisindole Alkaloid (−)-macrocarpamine 1 has been completed by coupling (−)-anhydromacrosalhine-methine 2 with plant-derived (+)-pleiocarpamine 3 in anhydrous 0.2 N HCl in THF in 75% yield.
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a partial synthesis of the alstonia Bisindole Alkaloid villalstonine
Tetrahedron Letters, 1994Co-Authors: James M Cook, Philip W LequesneAbstract:Abstract The partial synthesis of villalstonine 1 has been completed by coupling the macroline equivalent 2a with plant-derived (+)-pleiocarpamine 3 in 0.2N aq. hydrochloric acid in the presence of fluoride ion.
Michel Frederich - One of the best experts on this subject based on the ideXlab platform.
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in vivo antimalarial and antitrypanosomal activity of strychnogucine b a Bisindole Alkaloid from strychnos icaja
Planta Medica, 2018Co-Authors: Claire Beaufay, Olivia Jansen, Cn Teijaro, Allison Ledoux, Annelise Bordignon, Senzhi Zhao, Rodrigo B Andrade, Joelle Quetinleclercq, Michel FrederichAbstract:Strychnogucine B is a Bisindole Alkaloid previously isolated from Strychnos icaja that possesses promising in vitro antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its in vivo antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a Plasmodium berghei murine model. In the Peters's 4-d suppressive test, this Alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate in vitro antitrypanosomal activity but no in vivo activity in an acute Trypanosoma brucei model. It was also inactive in vitro on Leishmania mexicana promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.
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strychnobaillonine an unsymmetrical Bisindole Alkaloid with an unprecedented skeleton from strychnos icaja roots
Journal of Natural Products, 2014Co-Authors: Alembert T Tchinda, Monique Tits, Luc Angenot, Georges Dive, Olivia Jansen, Jeannoel Nyemb, Michel FrederichAbstract:A reinvestigation of the roots of Strychnos icaja resulted in the isolation of a new Bisindole Alkaloid named strychnobaillonine (1) with original C-17–N-1′ and C-23–C-17′ junctions, in addition to sungucine, bisnordihydrotoxiferine, and strychnohexamine (2). Compound 1 showed potent activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum in vitro with an IC50 value of 1.1 μM. The structures of the compounds were defined by detailed spectroscopic analyses, especially 1H and 13C NMR, DEPT, HSQC, COSY, NOESY, HMBC, and HRESIMS. The proposed absolute configuration was based on biosynthetic considerations and spectroscopic data (CD, NMR) supported by molecular modeling.
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dimeric Bisindole Alkaloids from the stem bark of strychnos nux vomica l
Phytochemistry, 2013Co-Authors: Mariecaroline Jonville, Joanne Bero, Monique Tits, Luc Angenot, Georges Dive, Evelyne Ollivier, Michel FrederichAbstract:Strychnos nux-vomica L. (Loganiaceae) is famous for its monomeric Alkaloid content, such as strychnine, a convulsant poison. The stem bark of the tree is traditionally used to treat intermittent fever in South East Asia. In various studies, it appeared that dimeric indolo-monoterpenic Alkaloids possess a promising activity on Plasmodium falciparum. Three bisindolomonoterpenic Alkaloids together with strychnochrysine, previously identified in the root bark of S. nux-vomica, were isolated from the stem bark. The structures of these compounds were established using NMR spectroscopy and mass spectrometry. Stereochemistry of the compounds was confirmed by molecular modelling. This then allowed the structural determination of strychnoflavine, a coloured Bisindole Alkaloid previously isolated from the root bark of the tree. Moreover, the conformational inversion in Alkaloids possessing an ether bond in the strychnane moiety could be easily predicted by specific δ 13 C NMR values. These longicaudatine-type Alkaloids were found to display in vitro antiplasmodial activity against a chloroquine resistant strain and a chloroquine sensitive strain. The most interesting was strychnochrysine showing an IC 50 value at around 10 μM. © 2012 Elsevier Ltd. All rights reserved.
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10'-Hydroxyusambarensine, a new antimalarial Bisindole Alkaloid from the roots of Strychnos usambarensis.
Journal of natural products, 1999Co-Authors: Michel Frederich, Viviane Brandt, Monique Tits, Gabriel Llabres, Jacques Penelle, Marie-pierre Hayette, Patrick Demol, Luc AngenotAbstract:Reinvestigation of Strychnos usambarensis Gilg resulted in the isolation of a tertiary phenolic Bisindole Alkaloid, 10'-hydroxyusambarensine (1), which was identified by detailed spectroscopic methods. Compound 1 was moderately active against two strains of Plasmodium falciparum in vitro.
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Guiaflavine, a new Bisindole quaternary Alkaloid from the stem bark of Strychnos guianensis.
Journal of natural products, 1999Co-Authors: Jacques Penelle, Viviane Brandt, Monique Tits, Michel Frederich, Philippe Christen, Luc AngenotAbstract:A reinvestigation of Strychnos guianensis resulted in the isolation of a colored quaternary Bisindole Alkaloid from the stem bark. The structure of this new substance, guiaflavine (1), was defined by detailed spectroscopic methods and comparison with model compounds.
Kanki Komiyama - One of the best experts on this subject based on the ideXlab platform.
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angustilobine and andranginine type indole Alkaloids and an uleine secovallesamine Bisindole Alkaloid from alstonia angustiloba
Phytochemistry, 2011Co-Authors: Shin-jowl Tan, Yun-yee Low, Kanki Komiyama, Toh-seok KamAbstract: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.
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leucophyllidine a cytotoxic Bisindole Alkaloid constituted from the union of an eburnan and a new vinylquinoline Alkaloid
Organic Letters, 2009Co-Authors: Chewyan Gan, Kanki Komiyama, W T Robinson, Tadahiro Etoh, Masahiko Hayashi, Toh-seok KamAbstract:A cytotoxic Bisindole Alkaloid possessing an unprecedented structure constituted from the union of an eburnan half and a novel vinylquinoline Alkaloid has been isolated from Leuconotis griffithii. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway to the novel quinolinic coupling partner is presented from an Aspidosperma precursor.
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bipleiophylline an unprecedented cytotoxic Bisindole Alkaloid constituted from the bridging of two indole moieties by an aromatic spacer unit
Organic Letters, 2008Co-Authors: Toh-seok Kam, Shin-jowl Tan, Kanki KomiyamaAbstract: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.
Xiao-dong Luo - One of the best experts on this subject based on the ideXlab platform.
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melodinine v an antitumor Bisindole Alkaloid with selective cytotoxicity from melodinus henryi
Bioorganic & Medicinal Chemistry Letters, 2016Co-Authors: Ya-ping Liu, Tao Feng, Yun-li Zhao, Grace Gar-lee Yue, Julia Kin-ming Lee, Clara Bik-san Lau, Xiao-dong LuoAbstract:Melodinine V (1) with a vincanol-eburenine skeleton, was isolated from Melodinus henryi. The structure was elucidated by extensive spectroscopic methods and further confirmed by the single crystal X-ray diffraction analysis. Melodinine V showed selective cytotoxic activities against human colon cancer cell line HT-29 and inhibited cell proliferation in a concentration-dependent manner. It induced cell cycle arrest at G1 phase and cellular apoptosis by increasing histone-associated DNA fragmentation in the treated HT-29 cells.
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Melodinine V, an antitumor Bisindole Alkaloid with selective cytotoxicity from Melodinus henryi.
Bioorganic & Medicinal Chemistry Letters, 2016Co-Authors: Ya-ping Liu, Tao Feng, Yun-li Zhao, Grace Gar-lee Yue, Julia Kin-ming Lee, Clara Bik-san Lau, Xiao-dong LuoAbstract:Melodinine V (1) with a vincanol-eburenine skeleton, was isolated from Melodinus henryi. The structure was elucidated by extensive spectroscopic methods and further confirmed by the single crystal X-ray diffraction analysis. Melodinine V showed selective cytotoxic activities against human colon cancer cell line HT-29 and inhibited cell proliferation in a concentration-dependent manner. It induced cell cycle arrest at G1 phase and cellular apoptosis by increasing histone-associated DNA fragmentation in the treated HT-29 cells. (C) 2016 Elsevier Ltd. All rights reserved.
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bisleuconothine a a Bisindole Alkaloid inhibits colorectal cancer cell in vitro and in vivo targeting wnt signaling
Oncotarget, 2016Co-Authors: Lingmei Kong, Tao Feng, Yuanyuan Wang, Chen Qing, Xiao-dong LuoAbstract:// Ling-Mei Kong 1, 2 , Tao Feng 1 , Yuan-Yuan Wang 3 , Xing-Yao Li 1, 4 , Zhen-Nan Ye 1, 2 , Tao An 1, 2 , Chen Qing 5 , Xiao-Dong Luo 1 , Yan Li 1 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China 2 University of the Chinese Academy of Sciences, Beijing 100049, China 3 Harbin Institute of Technology (Weihai), Weihai 264209, China 4 Present address: Georgia Regents University Health Sciences Campus, Augusta, Georgia 30912, USA 5 Kunming Medical University, Kunming 650500, China Correspondence to: Yan Li, e-mail: liyanb@mail.kib.ac.cn Xiao-Dong Luo, e-mail: xdluo@mail.kib.ac.cn Keywords: Bisleuconothine A, inhibitor, Wnt signaling, colorectal cancer cells Received: August 26, 2015 Accepted: January 23, 2016 Published: February 04, 2016 ABSTRACT Wnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer and small molecule antagonists of Wnt/β-catenin signaling are attractive candidates for developing effective therapeutics. In the present study, we identified Bisleuconothine A, a Bisindole Alkaloid with an eburnane-aspidosperma type skeleton, as a novel and selective Wnt signaling inhibitor by using a cell-based luciferase assay system. Our study found that Bisleuconothine A down-regulated the endogenous Wnt target gene expression through promoting phosphorylation of β-catenin and the subsequent inhibition of its nuclear translocation in HCT116 and SW480 colorectal cancer cells. In vitro , Bisleuconothine A inhibited cell proliferation through induction of apoptosis by increasing the cleavage of caspases in HCT116 and SW480 colorectal cancer cells. Moreover, in vivo , Bisleuconothine A dramatically suppressed tumor growth in HCT116 Xenograft. And further analysis showed that Bisleuconothine A suppressed the Wnt target gene expression in HCT116 Xenograft, which was associated with up-regulation of β-catenin phosphorylation and subsequent Wnt signaling inhibition. Taken together, our study indicated that Bisindole Alkaloids could be included as a new chemotype of small-molecule Wnt signaling inhibitors, and have great potential to be further developed for anti-tumor agents.
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Melosuavines A-H, Cytotoxic Bisindole Alkaloid Derivatives from Melodinus suaveolens
Journal of Natural Products, 2013Co-Authors: Ya-ping Liu, Gui-guang Cheng, Xiang-hai Cai, Tao Feng, Yun-li Zhao, Bao-hong Zhang, Xiao-dong LuoAbstract:Eight new Bisindole Alkaloids, melosuavines A C (1-3), having an aspidosperma-scandine linkage, melosuavines D F (4-6), possessing an aspidosperma-aspidosperma skeleton, and melosuavines G and H (7 and 8) of the aspidosperma-venalatonine type, tenuicausine (9), and melodinine J (10) were isolated from the twigs and leaves of Melodinus suaveolens. The structures of 1-8 were elucidated by extensive spectroscopic methods, and compounds 9 and 10 were identified by comparison with data in the literature. The relative configuration 9 was determined from the ROESY spectrum, and some NMR signals were reassigned. Compounds 1, 2, 4-6, 8, and 10 exhibited low micromolar cytotoxicity against one or more of five human cancer cell lines.
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gardovatine a novel strychnos strychnos Bisindole Alkaloid with cytotoxicity from gardneria oveta
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Tao Feng, Xiang-hai Cai, Ya-ping Liu, Bao-hong Zhang, Xiao-dong LuoAbstract:Gardovatine (1), the first Strychnos-Strychnos Alkaloid with a C-3/C-7 cleaved backbone, was isolated from twigs and leaves of Gardneria ovate, together with an analogue divarine (2). The structure was established by extensive spectroscopic methods. Both compounds showed potential cytotoxicities against five human cancer cell lines. (C) 2013 Elsevier Ltd. All rights reserved.