Showing papers on "Indole alkaloid published in 2016"
TL;DR: Alkaloids 1-16, 25-27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa and among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi.
Abstract: The new melokhanines A–J (1–10) and 22 known (11–32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B–H (2–8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1–16, 25–27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2–22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38–150 μM), i.e., half the efficacy of the positive control, griseofulvin.
84 citations
TL;DR: This review focuses on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes.
Abstract: Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid), saframycin (tetrahydroisoquinoline alkaloid), strictosidine (monoterpene indole alkaloid), ergotamine (ergot alkaloid) and opiates (benzylisoquinoline and morphinan alkaloid). This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details.
65 citations
TL;DR: Five new indole alkaloid glucosides named isatindigotindolosides A-E (1–5), along with three known analogs (6–8), were isolated from an aqueous extract of the Isatis indigotica roots based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations.
41 citations
TL;DR: The enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the Alstonia genus of the Apocynaceae family is reviewed.
Abstract: Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of monomeric indole alkaloids. Herein is reviewed the enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the Alstonia genus of the Apocynaceae family. The monomeric units belong to the sarpagine, ajmaline, macroline, vobasine, and pleiocarpamine series. An up-to-date discussion of their isolation, characterization, biological activity as well as approaches to their partial and total synthesis by means of both synthetic and biosynthetic strategies are presented.
40 citations
TL;DR: The results revealed that these inhibitory effects correlated with the suppressive effect of 4 and 7 on inducible nitric oxide synthase and cyclooxygenase-2 expression in LPS-stimulated BV2 cells.
35 citations
TL;DR: Alstorisine A (1), a normonoterpenoid indole alkaloid with 6/5/6/6 fused-ring system, regarded as a key intermediate from melodinine E to mersicarpine, was isolated from the cecidogenous leaves of Alstonia scholaris as mentioned in this paper.
32 citations
TL;DR: Analysis of perturbations in metabolism in these leaves demonstrated that amino acid metabolism was specifically activated by this binary stress, and the metabolic process to indole alkaloids in C. terniflora was enhanced after exposure to high level of UV-B irradiation followed by the dark.
Abstract: Indole alkaloids, which characteristically contain an indole nucleus, have pharmaceutical potential in a diverse range of applications. UV-B can elicit the accumulation of indole alkaloids. The indole alkaloid (6-hydroxyl-1H-indol-3-yl) carboxylic acid methyl ester with cytotoxic activity was found to accumulate in Clematis terniflora DC. leaves after exposure to high level of UV-B irradiation and the dark. However, a more in-depth analysis of the process behind this response has not yet been performed. Therefore, an integrated approach involving metabolomic, proteomic, and transcriptomic analyses is essential to detail the biosynthetic mechanisms of the regulation of indole alkaloid under binary stress. Indole alkaloid (6-hydroxyl-1H-indol-3-yl) carboxylic acid methyl ester was found to increase 7-fold in C. terniflora leaves post-treatment with high level of UV-B irradiation followed by an incubation in the dark compared with pre-treatment. Analysis by proteomics and metabolomics indicates a decrease in photosynthesis and carbohydrate metabolism, respectively. By contrast, amino acid metabolism was activated by this binary stress, and, specifically, the genes involved in the metabolic pathway converting shikimate to L-tryptophan were concurrently upregulated. Metabolites involved in indole biosynthesis (shikimate metabolic) pathway were anthranilate, indole, and L-tryptophan, which increased 2-, 441-, and 1-fold, respectively. In addition, there was an increase of 2- and 9-fold in L-serine deaminase (L-SD) and L-tryptophan synthase activity in C. terniflora leaves after exposure to high level of UV-B irradiation and the dark. (6-hydroxyl-1H-indol-3-yl) carboxylic acid methyl ester was found to increase in response to high level of UV-B irradiation followed by an incubation in the dark, implying that indole alkaloid biosynthesis was activated in C. terniflora leaves. Analysis of perturbations in metabolism in these leaves demonstrated that amino acid metabolism was specifically activated by this binary stress. In addition, an enhancement in serine level and L-SD activity was noted, which likely leads to an accumulation of pyruvate that, in turn, supplies shikimate metabolic pathway. The genes, metabolites, and L-tryptophan synthase activity that are involved in the metabolic pathway leading from shikimate to L-tryptophan all increased under the experimental binary stress, resulting in an enhancement of indole biosynthesis (shikimate metabolic) pathway. Therefore, the metabolic process to indole alkaloids in C. terniflora was enhanced after exposure to high level of UV-B irradiation followed by the dark.
25 citations
TL;DR: Kopsiyunnanine M is a new bisindole alkaloid consisting of two Strychnos-type alkaloids as mentioned in this paper, which has a 2,3,4,5-tetrahydro-1H-benzazepine skeleton.
24 citations
TL;DR: A new monoterpenoid indole alkaloid, kopsiyunnanine K, was isolated from Kopsia arborea and its intriguing rearranged structure and absolute configuration were determined on the basis of a 13-step asymmetric total synthesis.
24 citations
TL;DR: A new monoterpenoid indole alkaloid compound was discovered and evaluated for cytotoxicity against five cell lines (HEPG-2, A375, MDA-MB-231, SH-SY5Y, CT26).
24 citations
TL;DR: A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented and the structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine were confirmed by X-ray diffraction analysis.
Abstract: Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented.
TL;DR: A library of iridoid-conjugated indole alkaloid- like compounds was constructed from diversity-enhanced extracts, which constitutes an approach for increasing the chemical diversity of natural-product-like compounds by combining natural product chemistry and diversity-oriented synthesis.
TL;DR: Two new indole alkaloid derivatives (1, 2) together with six known indole alkaloids (3, 8) were isolated from the 70% EtOH/H2O extract of the stem of Naucleaofficinalis as discussed by the authors.
Abstract: Two new indole alkaloid derivatives (1, 2), together with six known indole alkaloids (3 – 8) were isolated from the 70% EtOH/H2O extract of the stem of Nauclea officinalis. Their structures were determined on the basis of extensive analyses of spectroscopic data (IR, MS, 1D- and 2D-NMR). All the isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7, and all the compounds showed significant inhibitory activities with the IC50 values of 0.82, 6.45, 9.75, 1.34, 3.40, 2.69, 1.58, and 1.96 μm, compared to the positive drug control group aminoguanidine with an IC50 value of 1.80 μm, especially compound 1 had the most significant activity.
TL;DR: It was concluded that T. alba and T. arborea are potentially viable sources of ibogaine and voacangine, and that these MIAs can be produced through somatic embryogenesis and whole plant regeneration of T.Alba.
Abstract: Tabernaemontana alba and Tabernaemontana arborea are Apocynaceae species used in Mexican traditional medicine for which little phytochemical information exists. In this study, preliminary gas chromatography/mass spectrometry analyses of different organs obtained from wild plants of both species identified a total of 10 monoterpenoid indole alkaloids (MIAs) and one simple indole alkaloid, nine of which were reported for the first time in these species. Furthermore, callus cultures were established from T. alba leaf explants and regeneration of whole plants was accomplished via somatic embryogenesis. The anti-addictive MIAs ibogaine and voacangine were then quantified by gas chromatography with flame ionization detection in wild plants of both species, as well as greenhouse-grown plants, in vitro-grown plantlets and embryogenic callus of T. alba. Ibogaine and voacangine were present in most samples taken from the whole plants of both species, with stem and root barks showing the highest concentrations. No alkaloids were detected in callus samples. It was concluded that T. alba and T. arborea are potentially viable sources of ibogaine and voacangine, and that these MIAs can be produced through somatic embryogenesis and whole plant regeneration of T. alba. Approaches to increase MIA yields in whole plants and to achieve alkaloid production directly in cell cultures are discussed.
TL;DR: One new indole alkaloid and one new indoles alkaloidal glycoside were isolated from the leaves of Evodia rutaecarpa and exhibited potent activity against Pseudomonas aeruginosa.
TL;DR: This is the first time that arginine has been found to be involved in the biosynthesis of bufotenines in parotid of toad.
Abstract: A new indole alkaloid named bufobutarginine (1), along with three known bufotenines, namely, serotonin (2), bufotenidine (3), and bufotenine (4), were isolated from the water extract of toad venom. Their structures were elucidated by spectral methods. This is the first time that arginine has been found to be involved in the biosynthesis of bufotenines in parotid of toad. The cytotoxic activities of these compounds have been assayed against A375 and A549 cell lines by the MTT method; however, they showed no cytotoxic activities.
TL;DR: In this paper, the indole alkaloid N-trans-feruloyl-3,5-dihydroxyindolin-2-one as a stereoisomeric mixture and the known alkaloids N -trans-p-coumaroy-l-tryptamine, Ntrans-pcoumaroysl-5-hydroxytryptamines (moschamine), from the ethyl acetate fraction of Croton echioides Baill.
Abstract: Bioguided fractionation of a hydroethanolic extract from the stem bark of Croton echioides Baill. led to isolation of the new indole alkaloid N-trans-feruloyl-3,5-dihydroxyindolin-2-one as a stereoisomeric mixture and the known alkaloids N-trans-p-coumaroyl-tryptamine, N-trans-pcoumaroyl-5-hydroxytryptamine, N-trans-4-methoxy-cinnamoyl-5-hydroxytryptamine, N-transferuloyl-5-hydroxytryptamine (moschamine), from the ethyl acetate fraction. The flavonoids 3-o-methyl kaempferol, 3-o-methyl quercetin, 3,7-di-o-methyl quercetin and 3,3’-di-o-methyl quercetin, together with the benzoic acid derivatives 4-hydroxybenzoic acid, 4-hydroxy-3methoxybenzoic acid and 4-hydroxy-3,5-dimethoxybenzoic acid were also isolated. Alkaloids and the flavonoids showed strong antioxidant properties in vitro radical scavenging assay (2,2-diphenyl1-picrylhydrazyl, DPPH), with IC50 values ranging from 9.2 to 17.5 µmol L -1 , lower than those of the positive control Trolox (IC50 = 17.9 µmol L -1 ). Alkaloids showed cytotoxic activity against the HCT-116 human cancer cell line, with IC50 values ranging from 86.8 to 210.7 µmol L -1 . Compound N-trans-4-methoxy-cinnamoyl-5-hydroxytryptamine was the most active, with an IC50 value of 86.8 µmol L -1
TL;DR: A new strychnine alkaloid was isolated from the leaves of Psychotria pilifera and exhibited potent antibacterial activity against Escherichia coli, equivalent to cefotaxime with MIC value of 0.781 μg/ml.
TL;DR: The precursor‐directed incorporation of cyanidin into a new 3′‐hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulin, one of the most unusual flavonoid‐indole hybrid structures that occur in nature.
Abstract: Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid-indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l-tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor-directed incorporation of cyanidin into a new 3'-hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins.
TL;DR: The identification, molecular cloning and functional expression in Escherichia coli of two R. serpentinacDNAs that are part of a recently discovered γ-tocopherol-like N- methyltransferase (γ-TLMT) family and are involved in indole and side-chain N-methylation of ajmaline are reported.
Abstract: Ajmaline biosynthesis in Rauvolfia serpentina has been one of the most studied monoterpenoid indole alkaloid (MIA) pathways within the plant family Apocynaceae. Detailed molecular and biochemical information on most of the steps involved in the pathway has been generated over the last 30 years. Here we report the identification, molecular cloning and functional expression in Escherichia coli of two R. serpentinacDNAs that are part of a recently discovered γ-tocopherol-like N-methyltransferase (γ-TLMT) family and are involved in indole and side-chain N-methylation of ajmaline. Recombinant proteins showed remarkable substrate specificity for molecules with an ajmalan-type backbone and strict regiospecific N-methylation. Furthermore, N-methyltransferase gene transcripts and enzyme activity were enriched in R. serpentina roots which correlated with accumulation of ajmaline alkaloid. This study elucidates the final step in the ajmaline biosynthetic pathway and describes the enzyme responsible for the formation of Nβ -methylajmaline, an unusual charged MIA found in R. serpentina.
TL;DR: Two new chromone derivatives and a new isocoumarin derivative are isolated from sponge-derived fungal strain Clonostachys sp.
Abstract: Two new chromone derivatives, 2-hydroxymethyl-3-methyl-7-methoxychromone (1) and 2-hydroxymethyl-3-tert-butyl-7-methoxychromone (2), together with a related known compound, 2,3-dimethyl-7-methoxychromone (3), were isolated from Rhinocladiella sp. (102), a fungus obtained from the sponge Ircinia oros. Furthermore, a new isocoumarin derivative, 3-(3-chloro-2-hydroxypropyl)-8-hydroxy-6-methoxy-isochromen-I-one (4) and a known analogue 3-[(R)- 3,3-dichloro-2-hydroxypropyl]-8-hydroxy-6-methoxy-IH-isochromen-I -one (dichlorodiaportin, 5), were identified from sponge-derived fungal strain Clonostachys sp. (AP4.1), while a new indole alkaloid 1-(4-hydroxybenzoyl)indole-3-carbaldehyde (6) was obtained from the sponge-derived fungus Engyodontium album (IVB lb). The structures of these compounds were established by NMR spectroscopic and mass spectrometric data analysis, as well as by comparison with literature reports. Compounds 4 and 6 were examined for cytotoxic and antimicrobial activities, respectively. None of them showed potent activity.
TL;DR: Ten indole alkaloids were obtained from an antifungal extract of Winchia calophylla, of which two were new, and N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indoles alkaloid, an unusual zwitterion with a basic vincorine- type skeleton.
Abstract: Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively.
TL;DR: The first total synthesis of 16-hydroxy-16,22-dihydroapparicine was completed, by combining a phosphine-mediated cascade reaction, diastereoselective nucleophilic addition of 2-acylindole or methylketone via a Felkin–Anh transition state, and chirality transferring intramolecular Michael addition.
Abstract: 5-Nor stemmadenine alkaloids, isolated from the genus Tabernaemontana, display a range of bioactivity. 16-Hydroxy-16,22-dihydroapparicine, the active component of an extract from the Tabernaemontana sp. (dichotoma, elegans, and divaricate), exhibited potent antimalarial activity, representing the first such report of the antimalarial property of 5-nor stemmadenine alkaloids. We, therefore, decided to attempt the total synthesis of the compound to explore its antimalarial activity and investigate structure and bioactivity relationships. As a result, we completed the first total synthesis of 16-hydroxy-16,22-dihydroapparicine, by combining a phosphine-mediated cascade reaction, diastereoselective nucleophilic addition of 2-acylindole or methylketone via a Felkin-Anh transition state, and chirality transferring intramolecular Michael addition. We also clarified the absolute stereochemistries of the compound. Furthermore, we evaluated the activity of the synthetic compound, as well as that of some intermediates, all of which showed weak activity against chloroquine-resistant Plasmodium falciparum (K1 strain) malaria parasites.
TL;DR: A new indole alkaloid strychnosinol and a new phenolic-glycoside were isolated from the bark and leaves of Strychno fendleri Sprague & Sandwith, together with six known compounds reported for the first time in this species.
Patent•
20 Apr 2016
TL;DR: In this paper, a novel indole alkaloid compound and a preparation method and a medical application thereof are described. But the method is not suitable for breast cancer patients, as it requires the extraction, separation and purification of dry tubers of rhizoma corydalis.
Abstract: The invention discloses a novel indole alkaloid compound and a preparation method and a medical application thereof. The compound is reported for the first time, is an indole alkaloid compound with a novel structure, and can be obtained by extracting, separating and purifying from dry tubers of rhizoma corydalis. The research proves that the compound is capable of lowering the proliferative activity of breast cancer cells and significantly suppressing proliferation, displays relatively high in vitro cytotoxicity, has an in vitro anti-breast cancer effect, and can be further developed into medicines for treating a breast cancer.
03 Nov 2016
TL;DR: Two new indole alkaloid derivatives namely Mostueatecine A (1), Mostueatesine B (2) and one triterpene derivative MostueATEcine C (3) were isolated from the stem and leaves of Mostuea batesii, along with five known compounds: Camptothecine (4), β-amyrin-3-Oglucopyranoside (5), Oleanolic acid (6), 2α,3α,19α-trihydroxy-24-norurs-4
Abstract: Two new indole alkaloid derivatives namely Mostueatecine A (1), Mostueatecine B (2) and one new triterpene derivative Mostueatecine C (3) were isolated from the stem and leaves of Mostuea batesii, along with five known compounds: Camptothecine (4), β-amyrin-3-O-glucopyranoside (5), Oleanolic acid (6), 2α,3α,19α-trihydroxy-24-norurs-4(23),12-dien-28-oic acid (7) and Saccharose(8). The structures of these compounds were elucidated using a detailed analysis of their HRESI-MS, 1D and 2D NMR spectroscopic data. Some of these compounds were evaluated in vitro for their antimicrobial activities against a wide range of microorganisms. The results showed that none of them possess noticeable activity.
Dissertation•
18 Aug 2016
TL;DR: This chapter concludes with a discussion of the implications of the data obtained in the second instalment of this large-scale study of central nervous system disorders in the context of a youth-services agency.
Abstract: ................................................................................................................................................. ii ACKNOWLEDGEMENTS .......................................................................................................................... v 1. CHAPTER 1 CONCLUSIONS ................................................................................................................. 1 REFERENCES .............................................................................................................................................. 3
Patent•
09 Nov 2016
TL;DR: In this paper, a novel indole alkaloid compound, a preparation method and a medical application thereof, was disclosed, which can be extracted from dried root of turnip, then separated, and purified.
Abstract: The invention discloses a novel indole alkaloid compound, a preparation method and a medical application thereof. The compound is firstly reported, is the indole alkaloid compound with a novel structure, and can be extracted from dried root of turnip, then separated, and purified. The in-vitro tests prove that the compound can inhibit the renal carcinoma cell line RC-2 propagation, the inhibition presents concentration and time dependence, and the compound can be used for developing the medicines for treating kidney cancer.