Rigorous Biogenetic Network for a Group of Indole Alkaloids Derived from Strictosidine

Szabó, László

doi:10.3390/molecules13081875

Cited by 96 publications

(75 citation statements)

References 25 publications

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“…Presumably 1 and 2 appears to be biogenetically analogous to mitragynine-type alkaloid dihydrocadambine (Brown and Fraser, 1974) with the unusual N-4 –C-18 bond (i.e., using mitragynine carbon numbering system) in a seven-membered ring. Therefore, the biogenetic pathway for 1( R )-banistenoside A and −B can be envisioned from the precursor of indole alkaloids 3α-H strictosidine via 3α-H epoxystrictosidine, followed by trioxoaglycone (Szabó, 2008), which undergoes extensive decrboxylation, cyclyzation, oxidation and glycoxylation to 1 and 2 . Interestingly, a synthetic azepinotetrahydro-β-carboline [CAS 610782-531] related to the compounds 1 or 2 demonstrated potent α2-adrenoceptor activity (Din Belle et al, 2003), therefore, further biological work on 1 and 2 is warranted.…”

Section: Discussionmentioning

confidence: 99%

Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease

Samoylenko

Rahman

Tekwani

et al. 2010

Journal of Ethnopharmacology

126

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Aim of the study-Parkinson's disease is a neurological disorder mostly effecting the elder population of the world. Currently there is no definitive treatment or cure for this disease. Therefore, in this study the composition and constituents of the aqueous extract of B. caapi for monoamine oxidases (MAO) inhibitory and antioxidant activities were assessed, which are relevant to the prevention of neurological disorders, including Parkinsonism.Materials and methods-The aqueous extract of B. caapi stems was standardized and then fractionated using reversed-phase (RP) chromatography. Pure compounds were isolated either by reversed-phase (RP) chromatography or centrifugal preparative TLC, using a Chromatotron ® . Structure elucidation was carried out by 1D and 2D NMR, Mass, IR and Circular Dichroism spectroscopy and chemical derivatization. Chemical profiling of the extract was carried out with RP-HPLC. The inhibitory activity of MAO-A, MAO-B, acetylcholinesterase, butyrylcholinesterase and catechol-O-methyl transferase enzymes, as well as antioxidant and cytotoxic activities of both B. caapi extract and isolated compounds were evaluated.Results-An examination of the aqueous extracts of B. caapi cultivar Da Vine yielded two new alkaloidal glycosides, named banistenoside A (1) and banistenoside B (2), containing "azepino[1,2-a]tetrahydro-β-carboline" unique carbon framework. One additional new natural tetrahydronorharmine (4), four known β-carbolines harmol (3), tetrahydroharmine (5), harmaline (6) and harmine (7), two known proanthocyanidines (−)-epicatechin (8) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 10-13, 17, 18) were also prepared. Harmaline (6) and harmine (7) showed potent in vitro inhibitory activity against recombinant human brain monoamine oxidase (MAO) -A and -B enzymes (IC 50 2.5 and 2.0 nM, and 25 and 20 µM, respectively), and (−)-epicatechin (8) and (−)-procyanidin B2 (9) showed potent antioxidant and moderate MAO-B inhibitory activities (IC 50 <0.13 and 0.57 µg/mL, and 65 and 35 µM). HPLC analysis revealed that most of the dominant chemical and bioactive markers (1, 2, 5, 7-9) were present in high concentrations in dried bark of large branch. Analysis of regular/commercial B. caapi dried stems showed a similar qualitative HPLC pattern, but relatively low content of dominant markers 1, 2, 7, and 9, which led to decreased MAO inhibitory and antioxidant potency. NIH Public AccessAuthor Manuscript J Ethnopharmacol. Author manuscript; available in PMC 2011 February 3.Conclusion-Collectively, these results give additional basis to the existing claim of B. caapi stem extract...

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Section: Discussionmentioning

confidence: 99%

Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease

Samoylenko

Rahman

Tekwani

et al. 2010

Journal of Ethnopharmacology

126

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“…One example is Catharanthus roseus. Here, the iridoids are precursors for secologanin, which is then processed into clinically important alkaloids such as vinblastine or vincristine [43]. Interestingly, plants use a completely different enzyme family to oxidise 8-hydroxygeraniol.…”

Section: Discussionmentioning

confidence: 99%

Independently recruited oxidases from the glucose-methanol-choline oxidoreductase family enabled chemical defences in leaf beetle larvae (subtribe Chrysomelina) to evolve

et al. 2014

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Larvae of the leaf beetle subtribe Chrysomelina sensu stricto repel their enemies by displaying glandular secretions that contain defensive compounds. These repellents can be produced either de novo (iridoids) or by using plant-derived precursors (e.g. salicylaldehyde). The autonomous production of iridoids, as in Phaedon cochleariae, is the ancestral chrysomeline chemical defence and predates the evolution of salicylaldehyde-based defence. Both biosynthesis strategies include an oxidative step of an alcohol intermediate. In salicylaldehyde-producing species, this step is catalysed by salicyl alcohol oxidases (SAOs) of the glucose-methanol-choline (GMC) oxidoreductase superfamily, but the enzyme oxidizing the iridoid precursor is unknown. Here, we show by in vitro as well as in vivo experiments that P. cochleariae also uses an oxidase from the GMC superfamily for defensive purposes. However, our phylogenetic analysis of chrysomeline GMC oxidoreductases revealed that the oxidase of the iridoid pathway originated from a GMC clade different from that of the SAOs. Thus, the evolution of a host-independent chemical defence followed by a shift to a host-dependent chemical defence in chrysomeline beetles coincided with the utilization of genes from different GMC subfamilies. These findings illustrate the importance of the GMC multi-gene family for adaptive processes in plant-insect interactions.

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“…The first committed enzyme in the monoterpene indole alkaloid pathway is strictosidine synthase, which conjugates secologanin with tryptamine to produce strictosidine. Strictosidine is subsequently modified to produce over 2,500 known MIAs in many plants from several families (for review see [6], [7]). C. roseus (Madagascar periwinkle) produces over 100 different indole alkaloids including the clinically important alkaloids vinblastine and vincristine, anticancer agents that act by interfering with microtubule formation [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Development of Transcriptomic Resources for Interrogating the Biosynthesis of Monoterpene Indole Alkaloids in Medicinal Plant Species

et al. 2012

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The natural diversity of plant metabolism has long been a source for human medicines. One group of plant-derived compounds, the monoterpene indole alkaloids (MIAs), includes well-documented therapeutic agents used in the treatment of cancer (vinblastine, vincristine, camptothecin), hypertension (reserpine, ajmalicine), malaria (quinine), and as analgesics (7-hydroxymitragynine). Our understanding of the biochemical pathways that synthesize these commercially relevant compounds is incomplete due in part to a lack of molecular, genetic, and genomic resources for the identification of the genes involved in these specialized metabolic pathways. To address these limitations, we generated large-scale transcriptome sequence and expression profiles for three species of Asterids that produce medicinally important MIAs: Camptotheca acuminata, Catharanthus roseus, and Rauvolfia serpentina. Using next generation sequencing technology, we sampled the transcriptomes of these species across a diverse set of developmental tissues, and in the case of C. roseus, in cultured cells and roots following elicitor treatment. Through an iterative assembly process, we generated robust transcriptome assemblies for all three species with a substantial number of the assembled transcripts being full or near-full length. The majority of transcripts had a related sequence in either UniRef100, the Arabidopsis thaliana predicted proteome, or the Pfam protein domain database; however, we also identified transcripts that lacked similarity with entries in either database and thereby lack a known function. Representation of known genes within the MIA biosynthetic pathway was robust. As a diverse set of tissues and treatments were surveyed, expression abundances of transcripts in the three species could be estimated to reveal transcripts associated with development and response to elicitor treatment. Together, these transcriptomes and expression abundance matrices provide a rich resource for understanding plant specialized metabolism, and promotes realization of innovative production systems for plant-derived pharmaceuticals.

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Rigorous Biogenetic Network for a Group of Indole Alkaloids Derived from Strictosidine

Cited by 96 publications

References 25 publications

Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease

Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease

Independently recruited oxidases from the glucose-methanol-choline oxidoreductase family enabled chemical defences in leaf beetle larvae (subtribe Chrysomelina) to evolve

Development of Transcriptomic Resources for Interrogating the Biosynthesis of Monoterpene Indole Alkaloids in Medicinal Plant Species

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