Showing papers on "Indole alkaloid published in 2018"
TL;DR: Asperversiamides A-H (1-8), eight linearly fused prenylated indole alkaloids featuring an unusual pyrano[3,2- f]indole unit, were isolated from the marine-derived fungus Aspergillus versicolor and exhibited a potent inhibitory effect against iNOS with an IC50 value of 5.39 μM.
Abstract: Asperversiamides A-H (1-8), eight linearly fused prenylated indole alkaloids featuring an unusual pyrano[3,2- f]indole unit, were isolated from the marine-derived fungus Aspergillus versicolor. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and optical rotation (OR) calculations. The relative configuration of C-21 of iso-notoamide B was herein revised, and a new methodology for preliminarily determining if the relative configuration of the bicyclo[2.2.2]diazaoctane moiety of a spiro-bicyclo[2.2.2]diazaoctane-type indole alkaloid is syn or anti was developed. The anti-inflammatory activities of the isolated compounds were all tested, and of these compounds, 7 exhibited a potent inhibitory effect against iNOS with an IC50 value of 5.39 μM.
36 citations
TL;DR: Pushing the terpenoid indole alkaloid pathway metabolic flux towards dimeric alkaloids vinblastine and vincristine production by over-expressing the two upstream pathway genes tryptophan decarboxylase and strictosidine synthase at two different levels of cellular organization viz. callus and leaf tissues is carried out.
Abstract: Catharanthus roseus today occupies the central position in ongoing metabolic engineering efforts in medicinal plants. The entire multi-step biogenetic pathway of its very expensive anticancerous alkaloids vinblastine and vincristine is fairly very well dissected at biochemical and gene levels except the pathway steps leading to biosynthesis of monomeric alkaloid catharanthine and tabersonine. In order to enhance the plant-based productivity of these pharma molecules for the drug industry, cell and tissue cultures of C. roseus are being increasingly tested to provide their alternate production platforms. However, a rigid developmental regulation and involvement of different cell, tissues, and organelles in the synthesis of these alkaloids have restricted the utility of these cultures. Therefore, the present study was carried out with pushing the terpenoid indole alkaloid pathway metabolic flux towards dimeric alkaloids vinblastine and vincristine production by over-expressing the two upstream pathway genes tryptophan decarboxylase and strictosidine synthase at two different levels of cellular organization viz. callus and leaf tissues. The transformation experiments were carried out using Agrobacterium tumefaciens LBA1119 strain having tryptophan decarboxylase and strictosidine synthase gene cassette. The callus transformation reported a maximum of 0.027% dry wt vindoline and 0.053% dry wt catharanthine production, whereas, the transiently transformed leaves reported a maximum of 0.30% dry wt vindoline, 0.10% catharanthine, and 0.0027% dry wt vinblastine content.
35 citations
TL;DR: Two monoterpenoid indole alkaloid erchinines, possessing unique 1,4-diazepine fused with oxazolidine architecture and three hemiaminals, were isolated from Ervatamia chinensis and exhibited significant antimicrobial activity against Trichophyton rubrum and Bacillus subtilis.
35 citations
TL;DR: A novel indole alkaloid glycoside with an unprecedented 2-(diphenylpropyl)indole skeleton, isatindigodiphindoside (1), was isolated from an aqueous extract of the roots of Isatis indigotica as mentioned in this paper.
32 citations
TL;DR: Three new prenylated indole 2,5-diketopiperazine alkaloids with nine known ones, one new indole alkaloid, and one new bis-benzyl pyrimidine derivative were isolated and characterized from the marine-derived fungus Eurotium sp.
Abstract: Three new prenylated indole 2,5-diketopiperazine alkaloids (1–3) with nine known ones (5–13), one new indole alkaloid (4), and one new bis-benzyl pyrimidine derivative (14) were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC50 values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.
26 citations
TL;DR: A comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthetic pathway, in response to tryptophan, secologanin and MeJA treatment is provided.
Abstract: Alkaloids are the main active ingredients in the medicinal plant Dendrobium officinale. Based on the published genomic and transcriptomic data, a proposed terpenoid indole alkaloid (TIA) biosynthesis pathway may be present in D. officinale. In this study, protocorm-like bodies (PLBs) with a high-yielding production of alkaloids were obtained by the optimization of tryptophan, secologanin and methyl jasmonate (MeJA) treatment. The results showed that the total alkaloid content was 2.05 times greater than that of the control group when the PLBs were fed with 9 µM tryptophan, 6 µM secologanin and 100 µM MeJA after 36 days. HPLC analysis showed that strictosidine synthase (STR) activity also increased in the treated plants. A total of 78 metabolites were identified using gas chromatography-mass spectrometry (GC-MS) in combination with liquid chromatography-mass spectrometry (LC-MS) methods; 29 differential metabolites were identified according to the multivariate statistical analysis. Among them, carapanaubine, a kind of TIA, exhibited dramatically increased levels. In addition, a possible underlying process of the metabolic flux from related metabolism to the TIA biosynthetic pathway was enhanced. These results provide a comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthesis, in response to tryptophan, secologanin and MeJA treatment.
25 citations
TL;DR: Among these last compounds, it could be established that addition of 19, 23 and 25 to MRP1-overexpressing cells led to glutathione depletion triggering cell death through apoptosis, and none of these compounds inhibited BCRP.
21 citations
TL;DR: This work has discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound.
Abstract: Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short-chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence-based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches.
17 citations
TL;DR: Five pairs of new 2-oxoindole alkaloids, (±)-peganumalines A-E (1-5), and a new indoles alkaloid, peganumaline F (6), along with two known analogues, were isolated from the seeds of Peganum harmala through spectroscopic analyses and quantum chemistry calculations.
16 citations
TL;DR: Three new bisindole alkaloids, bisleuconothines B-D (1-3), were isolated from the bark of Leuconotis griffithii and were deemed noncytotoxic when tested against A549 human lung adenocarcinoma cells.
Abstract: Three new bisindole alkaloids, bisleuconothines B–D (1–3), were isolated from the bark of Leuconotis griffithii. Their structures were elucidated by 1D and 2D NMR spectroscopy and DFT calculations. Bisleuconothine B (1) is the first monoterpene indole alkaloid dimer featuring bridges between both C-16–C-10′ and C-2–O–C-9′. All compounds were deemed noncytotoxic (IC50 > 10 μM) when tested against A549 human lung adenocarcinoma cells.
16 citations
TL;DR: Bioactivity evaluation reveals that functional group on indole nitrogen of 1 has a great effect on its cytotoxity, which provides a mean to probe the structure-activity relationships of 1.
Abstract: A novel indole alkaloid, misszrtine A (1), was isolated from marine sponge-derived fungus Aspergillus sp. SCSIO XWS03F03. The planar structure of 1 was assigned by analysis of spectroscopic data, the absolute configuration of which was unambiguously determined by total synthesis. Compound 1 represents the first example of N-isopentenyl tryptophan methyl ester with a phenylpropanoic amide arm, which exhibited a potent antagonistic activity on HL60 (IC50 = 3.1 μM) and LNCaP (IC50 = 4.9 μM) cell lines. Bioactivity evaluation reveals that functional group on indole nitrogen of 1 has a great effect on its cytotoxity, which provides a mean to probe the structure-activity relationships of 1.
TL;DR: Nauclorienine was a new indole alkaloid holding a rare corynanthe-type skeleton, and alkaloids 1–4 exhibited significant inhibitory effects against various human cancer cell lines with IC50 values comparable to those of cisplatin.
TL;DR: Reserpine is an indole alkaloid, antipsychotic, and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms.
TL;DR: A new indole alkaloid N′-formylserotonin was isolated from the water extract of traditional Chinese medicine Chansu and its structures were elucidated on the basis of spectral analyses.
TL;DR: Three new indole alkaloid derivatives, named paniculidines D‒F (1‒3), and six known analogs, were isolated from the roots of Murraya paniculata on the basis of comprehensive HRESIMS, UV, IR, and NMR spectroscopic data analysis and comparison with the data reported in literature.
TL;DR: The energetic viability of the Δ1-piperideine dimerizations under neutral and acidic conditions was assessed using the density functional theory computations and will be useful to narrow down the candidate genes involved in the Lys-derived alkaloid biosynthesis.
Abstract: Lys-derived alkaloids widely distributed in plant kingdom have received considerable attention and have been intensively studied; however, little is known about their biosynthetic mechanisms In terms of the skeleton formation, for example, of quinolizidine alkaloid biosynthesis, only the very first two steps have been identified and the later steps remain unknown In addition, there is no available information on the number of enzymes and reactions required for their skeletal construction The involvement of the Δ 1 -piperideine dimerization has been proposed for some of the Lys-derived alkaloid biosyntheses, but no enzymes for this dimerization reaction have been reported to date; moreover, it is not clear whether this dimerization reaction proceeds spontaneously or enzymatically In this study, the energetic viability of the Δ 1 -piperideine dimerizations under neutral and acidic conditions was assessed using the density functional theory computations In addition, a similar type of reaction in the dipiperidine indole alkaloid, nitramidine, biosynthesis was also investigated Our findings will be useful to narrow down the candidate genes involved in the Lys-derived alkaloid biosynthesis
TL;DR: Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C -10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.
Abstract: A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 μM and 0.43 μM, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.
TL;DR: A new indole alkaloid, pulveratinol (1), and two new anthranilic acid derivatives (2 and 3) were isolated from Indigo Pulverata Levis, together with 12 known compounds as discussed by the authors.
TL;DR: In this paper, a unique approach to the diketopiperazine indole alkaloid (±)-gliocladin C was developed and applied to formal syntheses of the related alkaloids T988C and GCLC.
TL;DR: N,N-dimethyltryptamine (DMT) was isolated and characterized from E. pungens roots, an unprecedented result since no indole alkaloid has been previously reported from Erythroxylaceae so far.
01 Jan 2018
TL;DR: This chapter provides condensed information about various MIAs, their biosynthesis in native plants, and contribution of HRCs to investigate the operational and regulatory mechanism of their in vitro and in planta biosynthesis.
Abstract: Terpene indole alkaloids (TIAs) comprise a major group of alkaloids as more than 3000 TIAs are known with resilient and beneficial biological activities. These TIAs exhibit varied structural intricacy with a characteristically common tryptophan or tryptamine residue with a carbon tail of terpenoid origin derived from the dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) pathways. According to the number of isoprene units, monoterpene indole alkaloids (MIAs) comprise the major class of TIAs that have two isoprene units originated from secologanin. MIAs have been extensively investigated for their immense pharmaceutical importance as these compounds possess strong properties against various types of cancers, diseases of the central nervous systems, malaria, hypertension, and major cardiac ailments. Keeping in mind their immense pharmaceutical worth and ever-increasing demand from the pharmaceutical world, solicitous attention is needed on their biological production and scientific strategies to abate the demand and supply ratio. Furthermore, a holistic understanding is always required to explore intimately interconnected facts of synthesis and regulation of these metabolites. In this context, with their reasonable competence, the hairy root cultures (HRCs) have gained center-stage focus as an excellent in vitro system for different scientific investigatory objectives. This chapter provides condensed information about various MIAs, their biosynthesis in native plants, and contribution of HRCs to investigate the operational and regulatory mechanism of their in vitro and in planta biosynthesis.
TL;DR: The obtained conjugates were screened in vitro for antioxidant and haemolytic activities, as well as for the protective effects against 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidativeHaemolysis of human erythrocytes.
TL;DR: Cong et al. as discussed by the authors reported the isolation and analysis of terpenoid indole alkaloids from Mappianthus iodoides Hand.-Mazz, and evaluated their cytotoxic activity against four human cancer cell lines, HT-29, MDA-MB-231, BEL-7402 and K-562, but were inactive.
TL;DR: This review provides a comprehensive overview on the achievements in the field of moschamine-related alkaloids and describes the different synthetic methodologies for the formation of key structural elements.
Abstract: Moschamine-related alkaloids originate mainly from feruloylserotonin by cyclization or dimerization. This review provides a comprehensive overview on the achievements in the field of moschamine-related alkaloids. In the isolation part, a detailed structural characterization of moschamine-related alkaloids is followed by their spectral data. Besides the well-known antioxidative activities, other screened biological properties are also outlined. Since their isolation, different protocols have been developed to synthesize these alkaloids. The synthetic part is organized according to the different synthetic methodologies for the formation of key structural elements.
Journal Article•
Patent•
28 Dec 2018
TL;DR: The indole polyketone alkaloids provided by the invention are compounds with a new skeleton; results of pharmacological experiments show that these compounds have inhibition activity on the proliferation of various tumor cells, in particular, can selectively inhibit tumor cells of MCF-7 and MDA-MB-231 as discussed by the authors.
Abstract: The invention discloses a class of indole polyketone alkaloids. The class of indole polyketone alkaloids is extracted from fermentation broth of daldinia eschscholzii IFB-TL01 coming from intestinal fungi of tenodera aridifolia sinensis fed with indole-3-methanol. The indole polyketone alkaloids provided by the invention are compounds with a new skeleton; results of pharmacological experiments show that the indole polyketone alkaloids have inhibition activity on the proliferation of various tumor cells, in particular, can selectively inhibit tumor cells of MCF-7 and MDA-MB-231, therefore, theindole polyketone alkaloids can be used as antitumor drugs, especially as a lead compound for the production of anti-breast cancer drugs, and are used in the antitumor drugs.
Patent•
16 Nov 2018
TL;DR: The indole alkaloid is extracted from fermentation liquid of gastrointestinal fungi IFB-TL01 (Daldinia eschscholzii) of tenodera aridifolia sinensis fed on indol-3methanol as discussed by the authors.
Abstract: The invention discloses indole alkaloid. The indole alkaloid is extracted from fermentation liquid of gastrointestinal fungi IFB-TL01 (Daldinia eschscholzii) of tenodera aridifolia sinensis fed on indol-3-methanol. The indole alkaloid Dalesindole B (compound 1) is a new compound, and the indole alkaloid Dalesindole C (compound 2) is a new skeleton compound. A pharmacological experimental result shows that the indole alkaloid has inhibition activity on the multiplication of various tumor cells, particularly can selectively inhibit HL-60 leukemia tumor cells, and can be used as an anti-tumor drug.