Indole alkaloids from Rauvolfia bahiensis A.DC. (Apocynaceae)

Kato, Lucília; Braga, Raquel Marques; Koch, Ingrid; Kinoshita, Luiza Sumiko

doi:10.1016/s0031-9422(02)00122-x

Cited by 31 publications

(22 citation statements)

References 15 publications

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“…The significant downfield shift for C-21 suggested that the sugar unit was adjacent to C-21, as supported by HMBC correlation from the anomeric proton of β-glucose at δ H 4.70 (d, J = 7.8 Hz) to C-21. Considering that it lacks an aldehyde group at C-16, which is usual for the sarpagine series such as 12-methoxy-vellosimine 16 or dihydroperaksine-17-al 11 from species of Rauvolfia, the 4,6-dimethyl-2-pyridyl moiety was assumed to be an artifact (produced by aldehyde-ammonia condensation reaction) linked to C-16 since acetone and NH 3 ·H 2 O were used as eluent during the isolation process. The above deduction was confirmed by HMBC correlations from H-5 and H-15 to C-17, and H-16 to C-17 and C-22.…”

Section: Resultsmentioning

confidence: 99%

Rauvotetraphyllines A-E, new indole alkaloids from Rauvolfia tetraphylla

Gao

Zhou²,

Kong

et al. 2012

Nat. Prod. Bioprospect.

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Section: Resultsmentioning

confidence: 99%

Rauvotetraphyllines A-E, new indole alkaloids from Rauvolfia tetraphylla

Gao

Zhou²,

Kong

et al. 2012

Nat. Prod. Bioprospect.

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“…It is especially rich in complex mixtures of monoterpenic indole alkaloids and several Brazilian native species have been chemically investigated being good candidates to furnish cholinesterase inhibitory compounds (Batina et al 2000, Batista et al 1996, Bolzani et al 1984, Cardoso and Vilegas 1999, Cardoso et al 1997, 1998, Kato et al 2002, Lemos et al 1996, Marques et al 1996, Medeiros et al 1999, Monnerat et al 2005, Pereira et al 2004, Rattmann et al 2005, Zocoler et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Two fast screening methods (GC-MS and TLC-ChEI assay) for rapid evaluation of potential anticholinesterasic indole alkaloids in complex mixtures

Vieira

Medeiros

Monnerat

et al. 2008

An. Acad. Bras. Ciênc.

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The pharmacotherapy for Alzheimer's disease (AD) includes the use of acetylcholinesterase inhibitors (AChEI). Recent investigations for novel AD therapeutic agents from plants suggested that Tabernaemontana genus is a promising source of novel anticholinesterasic indole alkaloids. In this work two fast screening techniques were combined in order to easily identify novel cholinesterase inhibitors (ChEI). Gas chromatography-mass spectrometry (GC-MS) of the less polar alkaloidic fractions obtained from the acid-base extraction of the stalk of T. laeta revealed thirteen monoindole alkaloids, four of them confirmed by co-injection with previously isolated alkaloids. The others were tentatively identified by mass fragmentation analysis. By gas chromatography with flame ionization detection (GC-FID) and using isatin as internal standard, affinisine and voachalotine were determined as major compounds. These fractions and fourteen previously isolated alkaloids, obtained from root bark of T. laeta and T. hystrix were investigated for acetyl (AChE) and butyrylcholinesterase (BuChE) inhibitory activities by the modified Ellman's method in thin layer chromatography (TLC-ChEI). Results showed selective inhibition of the alkaloids heyneanine and N b -methylvoachalotine for BuChE, and 19-epi-isovoacristine for AChE, whereas olivacine, affinisine, ibogamine, affinine, conodurine and hystrixnine inhibited both enzymes. In addition to confirming that monoterpenoid indole alkaloids can be novel therapeutic agents for AD, this is the first report of the ChEI activity of olivacine, a pyridocarbazole alkaloid.

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“…More assays with other strains should be done; however, the phytochemical methodology for isolation of the alkaloids must be repeated. This procedure comprises plant collection in the flowering season, December to February, chromatographic separation and purification, and spectroscopic analysis of the compounds (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

“…Monoterpene ␤-carboline alkaloids 1 through 3 were isolated from Psychotria prunifolia (26). Alkaloids 4 and 5 were isolated from Galianthe ramosa (27), alkaloids 6 and 7 were isolated from Rauvolfia bahiensis (28), and alkaloids 8 and 9 were isolated from Rauvolfia weddelianna (our unpublished data). The names of the alkaloids are as follows: 1, indolo[2,3-a]quinolizine-2-ethanol, 1,2,3,4,6,7,12,12b-octahydro-9-hydroxy-␤-vinyl; 2, indolo[2,3-a]quinolizine-2-ethanol, ␤-ethenyl-1,2,3,4,6,7,12,12b-octahydro-9-hydroxy-, 5-oxide; 3, strictosamide; 4, cyclopentanol, 3-ethenyl-1,-methyl-2-(5-methoxy-9H-pyrido [4,3-b]indol-4-yl); 5, cyclopentanol, 3-ethenyl-1,-methyl-2-(5, 7-dimethoxy-9H-pyrido [4,3-b]indol-4-yl); 6, 18-norajmalan-17,19-diol, 1,2-didehydro-1-demethyl-21-methyl-, 17-acetate; 7, Sarpagan-17-ol, 10-methoxy-; 8, reserpine; yohimban-16-carboxylic acid, 11,17-dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-, methyl ester; and 9, yohimban-16-carboxylic acid, 17-hydroxy-, methyl ester.…”

mentioning

confidence: 87%

Alkaloids as Inhibitors of Malate Synthase from Paracoccidioides spp.: Receptor-Ligand Interaction-Based Virtual Screening and Molecular Docking Studies, Antifungal Activity, and the Adhesion Process

Costa

Neto

Gonçalves

et al. 2015

Antimicrob Agents Chemother

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Paracoccidioides is the agent of paracoccidioidomycosis. Malate synthase plays a crucial role in the pathogenicity and virulence of various fungi, such as those that are human pathogens. Thus, an inhibitor of this enzyme may be used as a powerful antifungal without side effects in patients once these enzymes are absent in humans. Here, we searched for compounds with inhibitory capacity against the malate synthase of Paracoccidioides species (PbMLS). The three-dimensional (3D) structure of PbMLS was determined using the I-TASSER server. Compounds were selected from the ZINC database. Based on the mechanism underlying the interaction of the compounds with PbMLS, it was possible to identify ␤-carboline moiety as a standard key structure. The compounds with ␤-carboline moiety that are available in our laboratories were investigated. A total of nine alkaloid compounds were selected. The primary mechanisms of interaction of the alkaloid compounds in the binding pocket of PbMLS were identified and compared with the mechanism of interaction of acetyl coenzyme A (acetyl-CoA). We discovered that the amphipathic nature of the compounds, concomitant with the presence of ␤-carboline moiety, was crucial for their stability in the binding pocket of PbMLS. In addition, the importance of a critical balance of the polar and nonpolar contacts of the compounds in this region was observed. Four ␤-carboline alkaloid compounds showed the ability to inhibit recombinant PbMLS (PbMLSr) activity, Paracoccidioides species growth, and adhesion of the fungus and PbMLSr to the extracellular matrix components. The cytotoxicity of the alkaloids was also evaluated. Several plants, human-pathogenic fungi, and bacteria utilize the glyoxylate cycle during host infection (1). The unique enzymes of this cycle are isocitrate lyase and malate synthase. This pathway has not been observed in mammals; therefore, this cycle has been identified as a potential target for the discovery of new drugs. Novel active molecules should shorten the duration of chemotherapy, prevent the development of resistance, and eliminate latent disease.In the human-pathogenic fungi from the genus Paracoccidioides, the malate synthase (PbMLS) participates in the glyoxylate pathway, which enables the fungus to assimilate two-carbon compounds, and in the allantoin degradation pathway associated with purine metabolism, which allows the fungus to use nitrogen compounds (2). PbMLS is localized in peroxisomes and on the cell surface and is secreted. In addition, PbMLS plays a role as an adhesin, mediating the adhesion and internalization of the fungus to host cells (3). PbMLS is regulated during the transition from mycelium to yeast (4) and in oxidative stress (5). However, an inhibitor to PbMLS has not yet been investigated.In recent years, virtual screening has become an accepted tool in drug discovery that has successfully been applied in a number of therapeutic programs, particularly at the lead discovery stage, during which high-throughput molecular docking can play an important r...

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Indole alkaloids from Rauvolfia bahiensis A.DC. (Apocynaceae)

Cited by 31 publications

References 15 publications

Rauvotetraphyllines A-E, new indole alkaloids from Rauvolfia tetraphylla

Rauvotetraphyllines A-E, new indole alkaloids from Rauvolfia tetraphylla

Two fast screening methods (GC-MS and TLC-ChEI assay) for rapid evaluation of potential anticholinesterasic indole alkaloids in complex mixtures

Alkaloids as Inhibitors of Malate Synthase from Paracoccidioides spp.: Receptor-Ligand Interaction-Based Virtual Screening and Molecular Docking Studies, Antifungal Activity, and the Adhesion Process

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