The Experts below are selected from a list of 4065 Experts worldwide ranked by ideXlab platform
Toh-seok Kam - One of the best experts on this subject based on the ideXlab platform.
-
Conolodinines A–D, Aspidosperma–Aspidosperma Bisindole Alkaloids with Antiproliferative Activity from Tabernaemontana corymbosa
2019Co-Authors: Dawn Su-yin Sim, Siew-huah Lim, Yun-yee Low, Kae Shin Sim, 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
-
A Hexacyclic, Iboga-Derived Monoterpenoid Indole with a Contracted Tetrahydroazepine C-Ring and Incorporation of an Isoxazolidine Moiety, a Seco-Corynanthean, an Aspidosperma-Aspidosperma Bisindole with Anticancer Properties, and the Absolute Configu
Journal of natural products, 2016Co-Authors: Choy-eng Nge, Noel F. Thomas, Siew-huah Lim, Yun-yee Low, Kae Shin Sim, Toh-seok KamAbstract:Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that 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, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented.
-
A Hexacyclic, Iboga-Derived Monoterpenoid Indole with a Contracted Tetrahydroazepine C‑Ring and Incorporation of an Isoxazolidine Moiety, a Seco-Corynanthean, an Aspidosperma-Aspidosperma Bisindole with Anticancer Properties, and the Absolute Configu
2016Co-Authors: Choy-eng Nge, Noel F. Thomas, Siew-huah Lim, Yun-yee Low, Kae Shin Sim, Toh-seok KamAbstract:Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that 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, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented
-
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.
Thorsten Bach - One of the best experts on this subject based on the ideXlab platform.
-
pd ii catalyzed regioselective 2 alkylation of indoles via a norbornene mediated c h activation mechanism and applications
Journal of the American Chemical Society, 2012Co-Authors: Lei Jiao, Eberhardt Herdtweck, Thorsten BachAbstract:A palladium-catalyzed direct 2-alkylation reaction of free N-H indoles was developed based on a norbornene-mediated regioselective cascade C–H activation. The detailed reaction mechanism was investigated by NMR spectroscopic analyses, characterization of the key intermediate, deuterium labeling experiments, and kinetic studies. The results indicate that a catalytic cycle operates, in which an N-norbornene type palladacycle is formed as the key intermediate. Oxidative addition of alkyl bromide to the Pd(II) center in this intermediate is the rate-determining step of the reaction. The synthetic utility of this indole 2-alkylation method was demonstrated by its application in natural product total synthesis. A new and general strategy to synthesize Aspidosperma alkaloids was established employing the indole 2-alkylation reaction as the key step, and two structurally different Aspidosperma alkaloids, aspidospermidine and goniomitine, were synthesized in concise routes.
-
Pd(II)-Catalyzed Regioselective 2‑Alkylation of Indoles via a Norbornene-Mediated C–H Activation: Mechanism and Applications
2012Co-Authors: Lei Jiao, Eberhardt Herdtweck, Thorsten BachAbstract:A palladium-catalyzed direct 2-alkylation reaction of free N-H indoles was developed based on a norbornene-mediated regioselective cascade C–H activation. The detailed reaction mechanism was investigated by NMR spectroscopic analyses, characterization of the key intermediate, deuterium labeling experiments, and kinetic studies. The results indicate that a catalytic cycle operates, in which an N-norbornene type palladacycle is formed as the key intermediate. Oxidative addition of alkyl bromide to the Pd(II) center in this intermediate is the rate-determining step of the reaction. The synthetic utility of this indole 2-alkylation method was demonstrated by its application in natural product total synthesis. A new and general strategy to synthesize Aspidosperma alkaloids was established employing the indole 2-alkylation reaction as the key step, and two structurally different Aspidosperma alkaloids, aspidospermidine and goniomitine, were synthesized in concise routes
Xiang-hai Cai - One of the best experts on this subject based on the ideXlab platform.
-
trimeric and dimeric Aspidosperma type alkaloids from leaves of tabernaemontana divaricata dwaft
Bioorganic Chemistry, 2021Co-Authors: Jing Chen, Meifen Bao, Sumet Kongkiatpaiboon, Johann Schinnerl, Xiang-hai CaiAbstract:Abstract Continued interest in bioactive monoterpenoid indole alkaloids and the purpose to explore the artificial cultivation influence on the chemical composition in the same plant species, 8 undescribed Aspidosperma-type alkaloids including two unprecedented trimers, taberdivarines A–B (1–2), and six new dimers, taberdivarines C H (3–8), together with 9 known bisindoles were isolated from the leaves of Tabernaemontana divaricata 'Dwaft'. Notably, taberdivarines A and B were the first cases of Aspidosperma-Aspidosperma-Aspidosperma-type alkaloids with furan ring linkage patterns of the natural products. Their structures were elucidated by comprehensive spectroscopic analyse. Compounds 1–8 were screened for the cytotoxicity against three human cancer cell lines, SMMC-7721, HT-29 and A549. Among them, Compound 6 exhibited significant activity against three cell lines with IC50 values of 0.30, 0.75 and 3.41 μM, respectively (IC50 = 3.02, 0.14 and 2.23 μM for the positive control, vinorelbine). Compound 1, 3, 4, 6, 7 and 8 also expressed varying degrees of activity. The structure–activity relationships (SARs) of these alkaloids were discussed.
-
an Aspidosperma type alkaloid dimer from tabernaemontana bovina as a candidate for the inhibition of microglial activation
Organic chemistry frontiers, 2020Co-Authors: Simeng Zhao, Meifen Bao, Xiang-hai CaiAbstract:Twelve undescribed bisindole alkaloids, tabernaemontines A–L, were simultaneously isolated from the leaves of Tabernaemontana bovina and their structures were elucidated by spectroscopic methods. All alkaloids consist of two Aspidosperma-type units with various intramolecular linkages. Particularly, tabernaemontines A–D were assembled through C-3/14′ with a large angle strain, whilst tabernaemontines E–K adopted a preferential conformation. Tabernaemontine L was assembled via a C-14/10′ connection. Tabernaemontines F, K and L showed good inhibition of microglial activation. As a representative of Aspidosperma-type dimers, the P38 MAPK activation inhibition properties of tabernaemontine F were tested. The promising results revealed this compound as a potential candidate for the treatment of chronic neurodegenerative diseases.
-
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.
-
Melosuavines A–H, Cytotoxic Bisindole Alkaloid Derivatives from Melodinus suaveolens
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
Brian M Stoltz - One of the best experts on this subject based on the ideXlab platform.
-
enantioselective palladium catalyzed allylic alkylation reactions in the synthesis of Aspidosperma and structurally related monoterpene indole alkaloids
Natural Product Reports, 2018Co-Authors: Beau P Pritchett, Brian M StoltzAbstract:Covering: up to the end of 2017 Enantioselective Pd-catalyzed allylic alkylations of prochiral enolates represent a powerful tool for the construction of all-carbon quaternary stereocenters. This review describes the emergence of such reactions as strategic linchpins that enable efficient, stereocontrolled syntheses of Aspidosperma and related monoterpene indole alkaloids.
Alaide Braga De Oliveira - One of the best experts on this subject based on the ideXlab platform.
-
Aspidosperma species as sources of anti malarials uleine is the major anti malarial indole alkaloid from Aspidosperma parvifolium apocynaceae
Malaria Journal, 2015Co-Authors: Maria Fâni Dolabela, Renata Cristina De Paula, Alaide Braga De Oliveira, Marinete Marins Povoa, Geraldo Celio Brandao, Fabiola Dutra Rocha, Luciana Ferreira SoaresAbstract:Several species of the genus Aspidosperma (Apocynaceae) are used for the treatment of human malaria in Brazil and other meso- and South American countries. Ethanol extract from Aspidosperma parvifolium trunk bark was submitted to acid–base extractions leading to alkaloid and neutral fractions. The alkaloid fraction was chromatographed over a silica gel column. Ethanol extract, fractions and uleine were analysed by HPLC–DAD, UPLC-ESI–MS/MS and HPLC-ESI-MicroTOF-MS. The anti-malarial activity was assayed against resistant and sensitive chloroquine Plasmodium falciparum strains by microscopic, [3H]-hypoxanthine incorporation and HRPII techniques. Cytotoxicity (CC50) was evaluated against Vero and HepG2 cell lines by the MTT technique; selectivity indexes (SI = CC50/IC50) were calculated. The major peak in the HPLC–DAD chromatograms of the ethanol extract, alkaloid and neutral fractions suggested the presence of uleine that was isolated from the alkaloid fraction by column chromatography and was characterized by spectroscopic methods. A total of 15 alkaloids, besides uleine, were identified in the alkaloid fraction by UPLC-DAD-ESI–MS/MS and HPLC-ESI-MicroTOF-MS. The ethanol extract from Aspidosperma parvifolium and the neutral fraction were moderately active against P. falciparum strains. The alkaloid fraction and uleine disclosed high anti-malarial activity against chloroquine-resistant P. falciparum strain (IC50 300 µg/mL). The alkaloid fraction showed moderate cytotoxicity to HepG2 cell line (CC50 = 74.4 µg/mL). High SI values (>10) were determined for all samples. Ethanol extract from Aspidosperma parvifolium trunk bark afforded uleine that is the major constituent of the alkaloid fraction and disclosed a good in vitro anti-malarial activity. Moreover, 15 other indole alkaloids have been identified along with uleine.
-
Aspidosperma species as sources of antimalarials part iii a review of traditional use and antimalarial activity
Planta Medica, 2014Co-Authors: Renata Cristina De Paula, Maria Fâni Dolabela, Alaide Braga De OliveiraAbstract:Several plant species belonging to the genus Aspidosperma are traditionally used in Brazil and other Meso- and South American countries for the treatment of malaria and fevers. These traditional uses were motivation for this review. A literature survey completed for this review has identified scientific bibliographical references to the use of 24 Aspidosperma species to treat malaria/fevers and to 19 species that have had their extracts and/or alkaloids evaluated, with good results, for in vitro and/or in vivo antimalarial activity. Indole alkaloids are typical constituents of Aspidosperma species. However, only 20 out of more than 200 known indole alkaloids isolated from this genus have been assayed for antimalarial activity. These data support the potential of Aspidosperma species as sources of antimalarials and the importance of research aimed at validating their use in the treatment of human malaria.
-
in vitro antimalarial activity of six Aspidosperma species from the state of minas gerais brazil
Anais Da Academia Brasileira De Ciencias, 2012Co-Authors: Maria Fâni Dolabela, Marinete Marins Povoa, Salma Gomes De Oliveira, Jose Mario Velosos Peres, Jose Maria Nascimento, Alaide Braga De OliveiraAbstract:Ethnomedicinal informations point to some Aspidosperma species (Apocynaceae) as antimalarial plants in Brazil and have motivated the evaluation of six species which were collected in the state of Minas Gerais: A. cylindrocarpon Mull. Arg., A. parvifolium A. DC., A. olivaceum Mull. Arg., A. ramiflorum Mull. Arg., A. spruceanum Benth. ex Mull. Arg. and A. tomentosum Mart.. A total of 23 extracts of different plant parts in different solvents were assayed in vitro against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. All the extracts were shown to be active with IC50 values in the range of 5.0 ± 0 2.8 µg/mL to 65.0 ± 4.2 µg/mL. TLC profile of the extracts revealed the presence of alkaloids in the six species assayed. These results seem to confirm the popular use of Aspidosperma species to treat human malaria in Brazil and seem point to alkaloids as the putative active compounds of the assayed species.
