Showing papers on "Indole alkaloid published in 2015"
TL;DR: It is demonstrated how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism.
Abstract: The monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. There are ∼3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. The diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. Reconstitution of biosynthetic pathways in a heterologous host is a promising strategy for rapid and inexpensive production of complex molecules that are found in plants. Here, we demonstrate how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism. This system provides an important resource for developing the production of more complex plant-derived alkaloids, engineering of nonnatural derivatives, identification of bottlenecks in monoterpene indole alkaloid biosynthesis, and discovery of new pathway genes in a convenient yeast host.
361 citations
TL;DR: Nine new monoterpenoid indole alkaloids, ervatamines A-I (1-9), and five known ones (10-14), were isolated from Ervatamia hainanensis, and the new structures were elucidated by extensive spectroscopic analysis and comparison to known compounds.
Abstract: Nine new monoterpenoid indole alkaloids, ervatamines A–I (1–9), and five known ones (10–14), were isolated from Ervatamia hainanensis. The new structures were elucidated by extensive spectroscopic analysis and comparison to known compounds. Their absolute configurations were determined by various methods including computational methods, X-ray diffraction analysis, and electronic circular dichroism spectroscopy, as well as chemical transformations. Ervatamine A (1) is a ring-C-contracted ibogan-type monoterpenoid indole alkaloid with an unusual 6/5/6/6/6 pentacyclic rearranged ring system. Ervatamines B–E (2–5) display a nitrogen-containing 9/6 ring system, which is rarely observed in nature. The epimeric ervatamines B (2) and C (3) possess a 22-nor-monoterpenoid indole alkaloid carbon skeleton, which was only found in deformylstemmadenine. Compounds 10 and 14 exhibited significant anti-inflammatory activities, with IC50 values of 25.5 and 41.5 μM, respectively, while the IC50 value of indomethacin as a po...
67 citations
TL;DR: This study presents an integrated strategy that uses ultrahigh-performance liquid chromatography/linear ion-trap quadrupole/Orbitrap mass spectrometry coupled with in-house library data for the systematic characterization and discovery of new potentially bioactive molecules from indole alkaloids.
Abstract: The exploration of new chemical entities from herbal medicines may provide candidates for the in silico screening of drug leads. However, this significant work is hindered by the presence of multiple classes of plant metabolites and many re-discovered structures. This study presents an integrated strategy that uses ultrahigh-performance liquid chromatography/linear ion-trap quadrupole/Orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap-MS) coupled with in-house library data for the systematic characterization and discovery of new potentially bioactive molecules. Exploration of the indole alkaloids from Uncaria rhynchophylla (UR) is presented as a model study. Initially, the primary characterization of alkaloids was achieved using mass defect filtering and neutral loss filtering. Subsequently, phytochemical isolation obtained 14 alkaloid compounds as reference standards, including a new one identified as 16,17-dihydro-O-demethylhirsuteine by NMR analyses. The direct-infusion fragmentation behaviors of these isolated alkaloids were studied to provide diagnostic structural information facilitating the rapid differentiation and characterization of four different alkaloid subtypes. Ultimately, after combining the experimental results with a survey of an in-house library containing 129 alkaloids isolated from the Uncaria genus, a total of 92 alkaloids (60 free alkaloids and 32 alkaloid O-glycosides) were identified or tentatively characterized, 56 of which are potential new alkaloids for the Uncaria genus. Hydroxylation on ring A, broad variations in the C-15 side chain, new N-oxides, and numerous O-glycosides, represent the novel features of the newly discovered indole alkaloid structures. These results greatly expand our knowledge of UR chemistry and are useful for the computational screening of potentially bioactive molecules from indole alkaloids.
59 citations
TL;DR: Vindogentianine exhibited potential hypoglycemic activity in β-TC6 and C2C12 cells by inducing higher glucose uptake and significant in vitro PTP-1B inhibition, implying its therapeutic potential against type 2 diabetes.
58 citations
30 Jun 2015
TL;DR: Alkaloids are important therapeutic molecules due to their efficacy to prevent the onset of different degenerative diseases by scavenging the free radicals or binding with catalysts of the oxidative reactions, such as some metal ions.
Abstract: Plants are eminent source of new therapeutic agents that helps to alleviate human ailments and promote health. The noteworthy preventive and protective properties of these substances are related to their strong antioxidative, antimutagenic and anticarcinogenic potential. Among these, alkaloids are important secondary metabolites that are known to possess curative properties and are of prime importance for humankind. On the basis of their biosynthetic precursor and heterocyclic ring system, the compounds have been classified into different categories including indole, tropane, piperidine, purine, imidazole, pyrrolizidine, pyrrolidine, quinolizidine and isoquinoline alkaloids. These are important therapeutic molecules due to their efficacy to prevent the onset of different degenerative diseases by scavenging the free radicals or binding with catalysts of the oxidative reactions, such as some metal ions. These molecules also inhibit the growth and development of microorganisms including bacteria, fungi, protozoans etc. Due to their immense properties, these compounds are in great demand for pharmaceutical formulations and might emerge as valuable metabolite used to cure many lethal diseases like cancer. In this review, we aim to discuss about alkaloids, their biological activities and related mechanism of action for protective behaviour. Keywords: Alkaloids, Secondary metabolites, Indole alkaloid, Anticancer activities.
58 citations
TL;DR: In this article, eight monoterpenoid indole and quinoline alkaloids, scholarisines H-O (1-8), together with six known analogues, were isolated from seven-year stored leaves of Alstonia scholaris.
52 citations
TL;DR: The in vitro cytotoxic activities of these alkaloids against leukaemia HL-60 and prostate cancer PC-3 cell lines were evaluated.
51 citations
TL;DR: In this article, eleven indole alkaloids, alstoniascholarines A-K (1-11), along with one known analogue, were isolated from the aqueous fraction of Alstonia scholaris leaf extract.
49 citations
TL;DR: The results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus under UV-B irradiation and the induction of alkaloid biosynthesis appears to be responsive to binary stress.
Abstract: Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to the control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress.
48 citations
TL;DR: The stem bark of Anthocephalus cadamba has resulted in the isolation of anthocephaline, a new indole alkaloid, along with strictosamide, vincosamide and cadambine, which exhibited potent DNA topoisomerase IB inhibitory activity.
Abstract: Chemical investigation of the stem bark of Anthocephalus cadamba has resulted in the isolation of anthocephaline (1), a new indole alkaloid, along with strictosamide (2), vincosamide (3) and cadambine (4). The structures of the isolated alkaloids (1-4) were established by detailed 2D NMR spectral analysis. Cadambine (4) exhibited potent DNA topoisomerase IB inhibitory activity.
35 citations
TL;DR: The total synthesis of the tetracyclic indole alkaloid ht-13-A from commercially available (−)-4-amino-2-hydroxybutyric acid was reported in this article.
TL;DR: Alstonia scholaris F (1), a monoterpenoid indole alkaloid pigment with unprecedented carbon skeleton, and alstoscholarisine G (2) incorporated with a third nitrogen atom were isolated from the long-term stored leaves of Alstonia scholarsis as discussed by the authors.
TL;DR: The first microbial synthesis of a modified alkaloid, the first production of tetrahydrobiopterin in yeast, and the first use of a pterin-dependent mono-oxidation strategy for the synthesis of L-DOPA are presented.
Abstract: Monoterpene indole alkaloids (MIAs) have important therapeutic value, including as anticancer and antimalarial agents. Because of their chemical complexity, therapeutic MIAs, or advanced intermediates thereof, are often isolated from the native plants. The microbial synthesis of MIAs would allow for the rapid and scalable production of complex MIAs and MIA analogues for therapeutic use. Here, we produce the modified MIA hydroxystrictosidine from glucose and the monoterpene secologanin via a pterin-dependent mono-oxidation strategy. Specifically, we engineered the yeast Saccharomyces cerevisiae for the high-level synthesis of tetrahydrobiopterin to mono-oxidize tryptophan to 5-hydroxytryptophan, which, after decarboxylation to serotonin, is coupled to exogenously fed secologanin to produce 10-hydroxystrictosidine in an eight-enzyme pathway. We selected hydroxystrictosidine as our synthetic target because hydroxylation at the 10′ position of the alkaloid core strictosidine provides a chemical handle for the...
TL;DR: Ten new derivatives of dregamine and tabernaemontanine, two epimeric monoterpene indole alkaloids isolated from the methanol extract of the roots of TabernAemontana elegans, gave rise to ten new derivatives, showing promising apoptosis induction profile.
TL;DR: Ethanol extract from Aspidosperma parvifolium trunk bark afforded uleine that is the major constituent of the alkaloid fraction and disclosed a good in vitroAnti-malarial activity against resistant and sensitive chloroquine Plasmodium falciparum strains.
Abstract: 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.
TL;DR: Dalesindole isomerizes via a retro-Michael reaction to give stereoisomers with bioactivities, providing an access to new bioactive hybrids of fungal oligoketide with microbially decorated exogenous chemistry.
TL;DR: A new monoterpene indole alkaloid characterized by an unprecedented pentacyclic cage skeleton, arboridinine, was isolated from a Malaysian Kopsia species based on NMR, MS, and X-ray diffraction analysis.
TL;DR: This work describes a strategic approach for the synthesis of cyclohepta[b]indole structural scaffolds using a solvent-free Baylis-Hillman reaction of 2-bromobenzaldehydes and intramolecular Heck coupling reaction using Pd(OAc)2 as catalyst in the presence of benzyltrimethylammonium bromide under microwave condition.
Abstract: Ervatamine, silicine, methuenine, etc., are naturally occurring alkaloids that exhibit antimicrobial, anticancer, and anti-HIV activities. Indole fused with a seven-membered carbocyclic ring is a commonly observed structural feature among this series of bioactive compounds. This work describes a strategic approach for the synthesis of cyclohepta[b]indole structural scaffolds. The synthetic strategy consists of a solvent-free Baylis-Hillman reaction of 2-bromobenzaldehydes, followed by iodine-catalyzed C-alkylation of indole with the Baylis-Hillman adducts. Finally, intramolecular Heck coupling reaction using Pd(OAc)2 as catalyst in the presence of benzyltrimethylammonium bromide under microwave condition produced the desired cyclohepta[b]indole derivatives.
TL;DR: The potential of transgenic hairy root systems in modulating TIA production was confirmed and wild-type hairy roots accumulated significantly higher amounts of five alkaloids compared to non-transformed roots.
Abstract: Transgenic hairy roots of R. stricta were developed for investigation of alkaloid accumulations. The contents of five identified alkaloids, including serpentine as a new compound, increased compared to non-transformed roots. Rhazya stricta Decne. is a rich source of pharmacologically active terpenoid indole alkaloids (TIAs). In order to study TIA production and enable metabolic engineering, we established hairy root cultures of R. stricta by co-cultivating cotyledon, hypocotyl, leaf, and shoot explants with wild-type Agrobacterium rhizogenes strain LBA 9402 and A. rhizogenes carrying the pK2WG7-gusA binary vector. Hairy roots initiated from the leaf explants 2 to 8 weeks. Transformation was confirmed by polymerase chain reaction and in case of GUS clones with GUS staining assay. Transformation efficiency was 74 and 83% for wild-type and GUS hairy root clones, respectively. Alkaloid accumulation was monitored by HPLC, and identification was achieved by UPLC-MS analysis. The influence of light (16 h photoperiod versus total darkness) and media composition (modified Gamborg B5 medium versus Woody Plant Medium) on the production of TIAs were investigated. Compared to non-transformed roots, wild-type hairy roots accumulated significantly higher amounts of five alkaloids. GUS hairy roots contained higher amounts two of alkaloids compared to non-transformed roots. Light conditions had a marked effect on the accumulation of five alkaloids whereas the composition of media only affected the accumulation of two alkaloids. By successfully establishing R. stricta hairy root clones, the potential of transgenic hairy root systems in modulating TIA production was confirmed.
TL;DR: A highly oxygenated hexacyclic indole alkaloid, penicamedine A, bearing a rare furan ring, was isolated from the culture broth of Penicillium camemberti and elucidated by comprehensive spectroscopic analyses including NMR and HR‐ESI‐MS.
Abstract: A highly oxygenated hexacyclic indole alkaloid, penicamedine A (1), bearing a rare furan ring, was isolated from the culture broth of Penicillium camemberti, together with two known analogs, iso-α-cyclopiazonic acid (2) and cyclopiazonic acid (3). The structure of 1 was elucidated by comprehensive spectroscopic analyses including NMR and HR-ESI-MS. Its absolute configuration was further confirmed unambiguously by single-crystal X-ray diffraction analysis. Compound 1 was evaluated for anti-HIV activity with p24 assays and tested for cytotoxic activities against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, SW480, and the immortalized non-cancerous human pulmonary epithelial cell line BEAS-2B by MTS method.
TL;DR: In this paper, a group of indole alkaloids, gelsepyrrodines A−C (1, 2), with a new gelsedine skeleton incorporated with a pyrrole ring, were isolated from the roots of Gelsemium elegans Benth.
TL;DR: The results of this study showed that fractions of Ficus septica contain alkaloids including indole alkaloid or its derivatives and possess a cytotoxic effect on T47D cells, which supports the idea that alkal steroids in F. sePTica have anticancer activity.
Abstract: The study aimed to investigate the profile of alkaloids in two ethyl acetate soluble fractions, namely fractions A and B from an ethanolic extract of Ficus septica leaves and cytotoxic effect on T47D breast cancer cells Preparation of both fractions involved maceration of leaves with 70% (v/v) ethanol, filtration with Al2O3, precipitation with 01 N HCl, Mayer reagent, and 01 N NaOH, and also partition with ethyl acetate Qualitative thin layer chromatography (TLC) was conducted to determine the profile of alkaloids in the two fractions, using alkaloid specific reagents such as Dragendorff, sodium nitrite, and Van Urk-Salkowski Cytotoxic effects of both fractions on T47D cells were evaluated using MTT assay with a concentration series of 156; 312; 625; 125; 25 and 50 μg/mL The TLC test showed that fractions A and B contained alkaloids with Rx values of 074 and 080 for fraction A and 074, 084, 092 for fraction B with regard to yohimbine using the mobile phase of n-buthanol:glacial acetic acid:distilled water (3:1:1 v/v/v) Moreover, an indole alkaloid was detected with Rx values of 080 and 084, respectively Fractions A and B exhibited high cytotoxic effects on T47D cells with IC50 values of 257 and 273 μg/mL, respectively In conclusion, overall the results of this study showed that fractions of Ficus septica contain alkaloids including indole alkaloid or its derivatives and possess a cytotoxic effect on T47D cells This research supports the idea that alkaloids in F septica have anticancer activity
TL;DR: In this paper, the vobasine-iboga type bisindole alkaloid, voacalgine F (I) was isolated and structure elucidation was performed.
Abstract: isolation and structure elucidation of the new vobasine-iboga type bisindole alkaloid, voacalgine F (I)
TL;DR: An unprecedented bis-indole, a novel indole alkaloid, and some known indole-related compounds have been isolated from the sponge Plakortis sp. as discussed by the authors.
Abstract: An unprecedented bis-indole 1, a novel indole alkaloid 2, and some known indole-related compounds 3–5 have been isolated from the sponge Plakortis sp. collected from Zampa in Okinawa. Their structures were elucidated by spectroscopic analysis. These metabolites showed cytotoxic activity against P388 leukemia and B16 melanoma cells.
TL;DR: A new monoterpenoid indole alkaloid, 15,20-dehydro-3α-(2-oxopropyl) coronaridine, along with sixteen analogues, was isolated from the leaves of Catharanthus roseus cultivated in Yunnan on the basis of extensive spectroscopic analysis.
Abstract: A new monoterpenoid indole alkaloid, 15,20-dehydro-3α-(2-oxopropyl) coronaridine (1), along with sixteen analogues (2-17) were isolated from the leaves of Catharanthus roseus cultivated in Yunnan. The new alkaloid was elucidated on the basis of extensive spectroscopic analysis, and the known alkaloids were identified by comparison with the reported spectroscopic data. Among them, alkaloid 16 was isolated from Catharanthus for the first time.
01 Jul 2015-Heterocycles : an international journal for reviews and communications in heterocyclic chemistry
TL;DR: A new Nglucosylated indole alkaloid, 1-(1-β-glucopyranosyl)-3(hydroxymethyl)-1H-indole, along with five known compounds (3-7) were isolated from the trunk of B. koreana as discussed by the authors.
Abstract: A new N-glucosylated indole alkaloid, 1-(1-β-glucopyranosyl)-3(hydroxymethyl)-1H-indole (1) and a new O-serine glycoside, 3-O-α-Dxylopyranosyl-L-serine methyl ester (2), along with five known compounds (3-7) were isolated from the trunk of Berberis koreana. The structures of the new compounds were elucidated by 1D and 2D NMR data analysis and chemical reaction. Compounds 1, 2, 4, 5, and 7 reduced nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglial cell line. In addition, compounds 4 and 5 showed moderate anti-proliferative activity against A549 and HCT-15 cell lines. Berberis koreana Palib. (Berberidaceae), commonly known as ‘Korean barberry’, is an endemic species distributed throughout northern Korea. B. koreana has been used in Korean traditional medicine for the treatment of various disorders such as fever, gastroenteritis, sore throats, conjunctivitis, dysentery, jaundice, pneumonia, indigestion, and stomach aches.1 Various alkaloids with medicinal properties have been reported from the genus Berberis,2 and previous phytochemical investigations on B. koreana demonstrated the presence of alkaloids, including benzylisoquinoline and protoberberine derivatives as well as pyrrole acids.3-6 In our preliminary study, our group found that a MeOH extract of the trunk of B. koreana exhibited significant cytotoxicity against some human tumor cell lines, which has led us to investigate the MeOH extract.7-12 In the systematic study of B. koreana for its bioactive constituents, our HETEROCYCLES, Vol. 91, No. 7, 2015 1429
Patent•
04 Nov 2015
TL;DR: In this paper, the indole alkaloid has a good anti-tumor effect on gastric cancer and plays a certain role on liver cancer and breast cancer and is to become a novel anti-Tumor drug in the market.
Abstract: The invention discloses indole alkaloid and application thereof and belongs to the technical field of medicines. The structural formula of the indole alkaloid is shown in the description. Experimental data verify that the indole alkaloid has a good anti-tumor effect on gastric cancer and plays a certain role on liver cancer and breast cancer. The compound has the advantages of high efficiency and low toxicity and is to become a novel anti-tumor drug in the market.
Patent•
24 Jun 2015
TL;DR: In this article, a tetracyclic indole alkaloid derivative was used to inhibit alpha-glucosaccharase for the first time, thereby having a broad prospect in development and application of drugs for treating diabetes; meanwhile, the antineoplastic activity of a synthesized compound on human leukemia cells (K562) and human colon cancer cells (HT-29) is tested in the invention, and the result shows that the IC50 of this kind of derivatives is smaller than 100 uM.
Abstract: The invention relates to a tetracyclic indole alkaloid derivative as well as a preparation method and an application thereof. The structural formula is as follows. The invention finds that the tetracyclic indole alkaloid derivative can well inhibit alpha-glucosaccharase for the first time, thereby having a broad prospect in development and application of drugs for treating diabetes; meanwhile, the antineoplastic activity of a synthesized compound on human hepatoma cells (HepG2), human leukemia cells (K562) and human colon cancer cells (HT-29) is tested in the invention, and the result shows that the IC50 of this kind of derivatives is smaller than 100 uM. Compared with other anti-tumor drugs, the invention finds that the tetracyclic indole alkaloid derivative can kill tumor cells for the first time, and particularly can express good killing efficiency on the human leukemia cells (K562).
TL;DR: A pentacyclic indole alkaloid, kopsiyunnanine E, was isolated from Yunnan Kopsia arborea, and its structure, which was inferred from spectroscopic data, was established by a 16-step asymmetric total synthesis.
Abstract: A new pentacyclic indole alkaloid, kopsiyunnanine E, was isolated from Yunnan Kopsia arborea, and its structure, which was inferred from spectroscopic data, was established by a 16-step asymmetric total synthesis that proved that the natural alkaloid was not enantiomerically pure.