Showing papers on "Indole alkaloid published in 2009"
TL;DR: Diverse tryptophan derivatives and tryPTophan-containing cyclic dipeptides were accepted by these enzymes, providing a new strategy for convenient production of biologically active substances, e.g. by chemoenzymatic synthesis.
Abstract: Prenylated indole derivatives are hybrid natural products containing both aromatic and isoprenoid moieties and are widely spread in plants, fungi and bacteria. Some of these complex natural products, e.g. the ergot alkaloids ergotamine and fumigaclavine C as well as the diketopiperazine derivative fumitremorgin C and its biosynthetic precursors tryprostatin A and B, show a wide range of biological and pharmacological activities. Prenyl transfer reactions catalysed by prenyltransferases represent key steps in the biosynthesis of these compounds and often result in formation of products which possess biological activities distinct from their non-prenylated precursors. Recently, a series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from fungi. We have cloned and overexpressed six of these genes, fgaPT1, fgaPT2, ftmPT1, ftmPT2, 7-dmats and cdpNPT from A. fumigatus in E. coli and S. cerevisiae. The overproduced enzymes were characterised biochemically. Three additional prenyltransferases, DmaW-Cs, TdiB and MaPT were identified and characterised in a Clavicipitalean fungus, Aspergillus nidulans and Malbranchea aurantiaca, respectively. Sequence analysis and alignments with known aromatic prenyltransferases as well as phylogenetic analysis revealed that these enzymes belong to a new group of "aromatic prenyltransferases". They differ clearly from membrane-bound aromatic prenyltransferases from different sources and soluble prenyltransferases from bacteria. The characterised enzymes are soluble proteins, catalyse different prenyl transfer reactions on indole moieties of various substrates and do not require divalent metal ions for their enzymatic reactions. All of the enzymes accepted only dimethylallyl diphosphate as prenyl donor. On the other hand, they showed broad substrate specificity towards their aromatic substrates. Diverse tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by these enzymes, providing a new strategy for convenient production of biologically active substances, e.g. by chemoenzymatic synthesis.
103 citations
TL;DR: Brevianamide J, a new indole alkaloid dimer, was isolated together with four new diketopiperazine alkaloids from the solid-state fermented culture of Aspergillus versicolor and X-ray crystallographic analysis confirmed the structures of 1 and 4.
75 citations
TL;DR: A phytochemical study on Melodinus henryi has led to the isolation of two novel alkaloids, melohenines A and B, a monoterpenoid indole alkaloid with additional skeletal carbons arranged compactly in eight rings.
71 citations
TL;DR: A novel tetrakis monoterpene indole alkaloid, alasmontamine A, consisting of bis-vobtusine-type skeletons, was isolated from the leaves of Tabernaemontana elegans and exhibited moderate cell growth inhibitory activity against HL-60 cells.
41 citations
TL;DR: In this paper, three new alkaloids, 2′-O-β-D-glucopyranosyl-11-hydroxyvincoside lactam (1), 22 O-demethyl-22 O-β-, D-glocopyraniumsocorynoxeine (2), and (4S)-corynoxine Noxide (3) were isolated from the leaves of Uncaria rhynchophylla, together with four known tetracyclic oxindole or indole alkaloid glycos
Abstract: Three new alkaloids, 2′-O-β-D-glucopyranosyl-11-hydroxyvincoside lactam (1), 22-O-demethyl-22-O-β-D-glucopyranosylisocorynoxeine (2), and (4S)-corynoxeine N-oxide (3) were isolated from the leaves of Uncaria rhynchophylla, together with four known tetracyclic oxindole or indole alkaloids, isocorynoxeine N-oxide (4), rhynchophylline N-oxide (5), isorhynchophylline N-oxide (6), and dihydrocorynantheine (7), and an indole alkaloid glycoside, strictosidine (8). The structures of 1–3 were elucidated by spectroscopic methods including UV, IR, ESI-TOF-MS, 1D- and 2D-NMR, as well as CD experiments. The activity assay showed that 8 (IC50=8.3 μM) exhibited potent inhibitory activity on lipopolysaccharide(LPS)-induced nitrogen monoxide (NO) release in N9 microglia cells. However, only weak inhibitory activities were observed for 1–7 (IC50>100 μM for 1–6 or >30 μM for 7).
39 citations
TL;DR: Six of the nine compounds showed enhanced activity when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Erysotrine did not show cytotoxic activity by itself, but exhibited significant cytotoxicity when Combined with TRAIL.
28 citations
TL;DR: In this paper, two aza-tryptamine substrates were successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus.
23 citations
TL;DR: In this article, a new indole alkaloid, akuammidine-Noxide (1) was isolated from the leaves of Alstonia scholaris (Apocynaceae) together with akuamammidine (2), and the structure was elucidated by NMR spectral analysis and chemical correlation.
Abstract: A new indole alkaloid, akuammidine-N-oxide (1) was isolated from the leaves of Alstonia scholaris (Apocynaceae) together with akuammidine (2), and the structure was elucidated by NMR spectral analysis and chemical correlation. Akuammidine (2) showed a moderate antiplasmodial activity.
15 citations
01 Jan 2009
TL;DR: The amounts of certain terpenoid indole alkaloid metabolites, including the important vinblastine precursors, catharanthine and vindo line, were increased significantly and the regulatory nature of the biosynthetic network was invested.
Abstract: The important anticancer pharmaceuticals, vinblastine and vincristine, are produc ed by Catharanthus roseus. Given their cytotoxicity, these valuable alkaloids are produced in very small quantities within the aerial parts of the plant. The high cost of isola ting the drugs has led to research efforts to increase the alkaloid content of C. r seus cell cultures, tissue cultures, and seedlings. The metabolic engineering of C. roseus strives to overcome the strict regulation of the biosynthetic pathways. Seedlings of C. roseus were elicited with methyl jasmonate (MeJA) to induce expression of octadecanoid-responsive Catharanthus AP2-domain 3 (ORCA3), a transcription regulator of several biosynthetic genes. ORCA3 exhibited increases up to 25fold observed 0.5 h after MeJA treatment with the transcript levels of biosyntheti c genes following with variable timing. The amounts of certain terpenoid indole alkaloid (TI A) metabolites, including the important vinblastine precursors, catharanthine and vindo line, were increased significantly. Three hairy root cultures of C. roseus were investigated. The ASAB-1 line expressing a feedback-resistant anthranilate synthase (AS) α subunit from Arabidopsis under the control of a glucocorticoid-inducible promoter and an AS β subunit from Arabidopsis under the control of the constitutive CaMV 35S promoter, the EHIDXS-4-1 line express ing 1-deoxy-D-xylulose 5-phosphate synthase (DXS) under the control of a glucocor ti idinducible promoter, and the EHIT16H-34-1 line tabersonine 16-hydroxylase (T16H) under the control of a glucocorticoid-inducible promoter. These lines were used to investi gat the regulatory nature of the biosynthetic network by quantifying the effect of l ight-adaptation, biosynthetic enzyme overexpression, and the combination of these two factors on the
13 citations
TL;DR: A monoterpene indole alkaloid, naucleamide F (1), has been isolated from the bark and wood of Nauclea latifolia, and the structure and stereochemistry were elucidated on the basis of spectral data as mentioned in this paper.
Abstract: A new monoterpene indole alkaloid, naucleamide F (1), has been isolated from the bark and wood of Nauclea latifolia, and the structure and stereochemistry were elucidated on the basis of the spectral data. Naucleamide F (1) is a new monoterpene indole alkaloid consisting of a tetrahydro-β-carboline ring fused to a pyridone ring, and a 1,3,5-trioxepane ring fused to a dihydropyran ring and a glucose unit.
7 citations
TL;DR: In this article, a monoterpenoid indole alkaloid, 11-methoxybumamine-17-0-3',4,5'-trimethoxybenzoate (1), was isolated from Rauvolfia yunnanensis Tsiang.
TL;DR: A monoterpene indole alkaloid, naucleamide F (1), has been isolated from the bark and wood of Nauclea latifolia, and the structure and stereochemistry were elucidated on the basis of spectral data.
Abstract: A new monoterpene indole alkaloid, naucleamide F (1), has been isolated from the bark and wood of Nauclea latifolia, and the structure and stereochemistry were elucidated on the basis of the spectral data. Naucleamide F (1) is a new monoterpene indole alkaloid consisting of a tetrahydro-β-carboline ring fused to a pyridone ring, and a 1,3,5-trioxepane ring fused to a dihydropyran ring and a glucose unit.
TL;DR: In this paper, the leaves and stems of the Hunteria zeylanica were investigated for the isolation of indole alkaloid, 11-hydroxyrhazimanine (1), and nine known analogs 2−10.
Abstract: Investigation of the leaves and stems of Hunteria zeylanica resulted in the isolation of one new indole alkaloid, 11-hydroxyrhazimanine (1), and nine known analogs 2–10. Their structures were determined by 1D and 2D NMR analyses. Decarbomethoxydihydrogambirtannin (2), dihydroantirhine (3), and 3-oxomehranine (4) were isolated from Hunteria genus for the first time.
TL;DR: In this article, the first sulphur-containing indole alkaloid from the leaf extracts of Glycosmis petelotii collected in the north of Vietnam, was described from indole through 6 steps.
Dissertation•
01 May 2009
TL;DR: In this paper, the structure of indoles, indolines and bisindolines bearing C-2 aryl substituents are described in a parallel investigation on the leaves of Kopsia singapurensis.
Abstract: The phytochemical study on Apocynaeae family (Neisosperma oppositifolia and Kopsia singapurensis) involves extraction, separations by using various chromatographic methods and structural determination by spectroscopic techniques such as UV, IR, NMR including 1D-NMR (1H, 13C, and DEPT), 2D-NMR (COSY, NOESY, HMQC/HSQC, and HMBC)and MS (LCMS and HRESIMS). The structures of the compounds were also elucidated by comparison with previous work. Isolation studies on the bark of Neisosperma oppositifolia yielded oppositinine A 356, oppositinine B 357, isoreserpiline 90, isocarapanaubine 108, vobasine 358, 10- methoxydihydrocorynantheol-N-oxide 359 and ochropposinine oxindole 360. Oppositinine A 356 and oppositinine B 357 are new -carboline alkaloid and the others are known indole alkaloids. Eleven compounds were successfully isolated from the bark of Kopsia singapurensis of which one is a new indole alkaloid aspidofractinine type); namely 15-hydroxykopsinine-Noxide 364. The known compounds are venalstonine 163, venacarpine A 222, rhazinilam 3,pleiocarpamine 164, 16-epi-deacetylakuammiline 126, 15-hydroxykopsinine 361, 16- hydroxymethylpleiocarpamine 207, lonicerine 225, kopsinine-N-oxide 362 and 16-epideacetylakuammiline- N-oxide 363. Further investigation on the leaves of the same plant afforded three compounds. The compounds are singaporentine A 365, kopsifoline A 227 and kopsininic acid 240. Singaporentine A 365 is a new compound belonging to a rare type of indole alkaloid. At present, only six alkaloids possess this peculiar skeleton; kopsifoline A-F previously isolated from Kopsia fruticosa. In a parallel investigation, new methods for the construction of indoles, indolines and bisindolines bearing C-2 aryl substituents are described in this thesis.
TL;DR: A new Erythrinan alkaloid (1), erythodine Noxide, was isolated from the seeds of Erystrina velutina together with seven known EryTHrinan alkaloids (2-7, 9) and an indole alkalinoid (8) by spectroscopic methods as mentioned in this paper.
Abstract: A new Erythrinan alkaloid (1), erythodine N-oxide, was isolated from the seeds of Erythrina velutina together with seven known Erythrinan alkaloids (2-7, 9) and an indole alkaloid (8). The structure of new compound (1) was elucidated by spectroscopic methods. Six of the nine compounds showed enhanced activity when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Erysotrine (4) did not show cytotoxic activity by itself, but exhibited significant cytotoxicity when combined with TRAIL.
01 Dec 2009
TL;DR: This work shows that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus, and serves as a starting point to explore fermentation of aze-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.
Abstract: Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.
01 Jan 2009
TL;DR: Ibogaine is a naturally occurring psychoactive compound found in a number of plants, principally in a member of the dogbane family known as iboga (Tabernanthe iboga; Fig. 19). Bark ibogaine-containing preparations are used in medicinal and ritual purposes by African spiritual traditions of the Bwiti.
Abstract: Ibogaine is a naturally occurring psychoactive compound found in a number of plants, principally in a member of the dogbane family known as iboga (Tabernanthe iboga; Fig. 19). Bark Ibogaine-containing preparations are used in medicinal and ritual purposes by African spiritual traditions of the Bwiti, who claim to have learned it from the Pygmy. In recent times, it has been identified as having anti-addictive properties. Ibogaine is an indole alkaloid that is obtained either by extraction from the iboga plant or by semi-synthesis from the precursor compounds voacangine, another plant alkaloid. Although a full organic synthesis of ibogaine has been achieved but is too expensive and challenging to produce any commercially significant yield.
TL;DR: A new indole alkaloid, singaporentine A, together with two known alkaloids, kopsifoline A and kopsininic acid, were yielded by study on chemical constituents from the leaves of Kopsia singapurensis (Apocynaceae).
Abstract: Study on chemical constituents from the leaves of Kopsia singapurensis (Apocynaceae) yielded a new indole alkaloid, singaporentine A (1) together with two known alkaloids, kopsifoline A (2) and kopsininic acid (3). The structure of 1 was elucidated by combination of various spectroscopic methods such as MS, UV, IR, 1D and 2D NMR. Singaporentine A exhibited cytotoxic activity against P388 murine leukemia cells.