Showing papers on "Indole alkaloid published in 2022"
TL;DR: Indole alkaloids with a wide range of pharmacological bioactivities are important candidate drugs for organ fibrosis treatment through the suppression of inflammatory response, oxidative stress, TGF-β/Smad pathway, and other signaling pathways.
Abstract: Indole alkaloids are widely distributed in nature and have been particularly studied because of their diverse biological activities, such as anti-inflammatory, anti-tumor, anti-bacterial, and anti-oxidant activities. Many kinds of indole alkaloids have been applied to clinical practice, proving that indole alkaloids are beneficial scaffolds and occupy a crucial position in the development of novel agents. Fibrosis is an end-stage pathological condition of most chronic inflammatory diseases and is characterized by excessive deposition of fibrous connective tissue components, ultimately resulting in organ dysfunction and even failure with significant morbidity and mortality. Indole alkaloids and indole derivatives can alleviate pulmonary, myocardial, renal, liver, and islet fibrosis through the suppression of inflammatory response, oxidative stress, TGF-β/Smad pathway, and other signaling pathways. Natural indole alkaloids, such as isorhynchophylline, evodiamine, conophylline, indirubin, rutaecarpine, yohimbine, and vincristine, are reportedly effective in organ fibrosis treatment. In brief, indole alkaloids with a wide range of pharmacological bioactivities are important candidate drugs for organ fibrosis treatment. The present review discusses the potential of natural indole alkaloids, semi-synthetic indole alkaloids, synthetic indole derivatives, and indole-contained metabolites in organ fibrosis treatment.
17 citations
TL;DR: The binding modes and SARs investigations of synthetic indole derivatives, along with a brief mechanism on their anti-tubulin activity, are presented in this review.
Abstract: Tubulin inhibitors can interfere with normal cell mitosis and inhibit cell proliferation through interfering with the normal structure and function of microtubules, forming spindle filaments. Indole, as a privileged pharmacological skeleton, has been widely used in anti-cancer inhibitors. A variety of alkaloids containing an indole core obtained from natural sources have been proven to inhibit tubulin polymerization, and an ever-increasing number of synthetic indole-based tubulin inhibitors have been reported. Among these, several kinds of indole-based derivatives, such as TMP analogues, aroylindoles, arylthioindoles, fused indole, carbazoles, azacarbolines, alkaloid nortopsentin analogues and bis-indole derivatives, have shown good inhibition activities towards tubulin polymerization. The binding modes and SARs investigations of synthetic indole derivatives, along with a brief mechanism on their anti-tubulin activity, are presented in this review.
12 citations
TL;DR: The present data have shown that mitragynine is able to bind to opioid receptors, particularly MOR, to exhibit the analgesic effect and the updated pharmacological and toxicological properties of mitragyna speciosa and its diastereomers are discussed to render a comprehensive understanding of the pharmacological properties.
Abstract: Mitragynine, is a naturally occurring indole alkaloid that can be isolated from the leaves of a psychoactive medicinal plant. Mitragyna speciosa, also known as kratom, is found to possess promising analgesic effects on mediating the opioid receptors such as µ (MOR), δ (DOR), and κ (KOR). This alkaloid has therapeutic potential for pain management as it has limited adverse effect compared to a classical opioid, morphine. Mitragynine is frequently regarded to behave like an opioid but possesses milder withdrawal symptoms. The use of this alkaloid as the source of an analgesic candidate has been proven through comprehensive preclinical and clinical studies. The present data have shown that mitragynine is able to bind to opioid receptors, particularly MOR, to exhibit the analgesic effect. Moreover, the chemical and pharmacological aspects of mitragynine and its diastereomers, speciogynine, speciociliatine, and mitraciliatine, are discussed. It is interesting to know how the difference in stereochemical configuration could lead to the difference in the bioactivity of the respective compounds. Hence, in this review, the updated pharmacological and toxicological properties of mitragynine and its diastereomers are discussed to render a comprehensive understanding of the pharmacological properties of mitragynine and its diastereomers based on their structure–activity relationship study.
10 citations
TL;DR: In this article , an ultra-high performance liquid chromatography-high resolution mass spectrometry method was developed for the analysis of 8 indole alkaloids (7-hydroxymitragynine, ajmalicine, paynantheine, mitragynines, speciogynine, isopaynantheines, and speciociliatine) and 6 oxindole alphabets (isomitraphyllines, isospeciofoleine, speciofoline, Corynoxine A, corynoxeine, and rhynchophylline) in US-grown kratom plants and commercial products.
Abstract: Many consumers are turning to kratom (Mitragyna speciosa) to self-manage pain and opioid addiction. In the United States, an array of capsules, powders, and loose-leaf kratom products are readily available. Additionally, several online sites supply live kratom plants. A prerequisite to establishing quality control and quality assurance standards for the kratom industry, or understanding how alkaloid levels effect clinical outcomes, is the identification and quantitation of major and minor alkaloid constituents within available products and preparations. To this end, an ultra-high performance liquid chromatography-high resolution mass spectrometry method was developed for the analysis of 8 indole alkaloids (7-hydroxymitragynine, ajmalicine, paynantheine, mitragynine, speciogynine, isopaynantheine, speciociliatine, and mitraciliatine) and 6 oxindole alkaloids (isomitraphylline, isospeciofoleine, speciofoline, corynoxine A, corynoxeine, and rhynchophylline) in US-grown kratom plants and commercial products. These commercial products shared a qualitatively similar alkaloid profile, with 12 - 13 detected alkaloids and high levels of the indole alkaloid mitragynine (13.9 ± 1.1 - 270 ± 24 mg/g). The levels of the other major alkaloids (paynantheine, speciociliatine, speciogynine, mitraciliatine, and isopaynantheine) and the minor alkaloids varied in concentration from product to product. The alkaloid profile of US-grown M. speciosa "Rifat" showed high levels of the indole alkaloid speciogynine (7.94 ± 0.83 - 11.55 ± 0.18 mg/g) and quantifiable levels of isomitraphylline (0.943 ± 0.033 - 1.47 ± 0.18 mg/g). Notably, the alkaloid profile of a US-grown M. speciosa seedling was comparable to the commercial products with a high level of mitragynine (15.01 ± 0.20 mg/g). This work suggests that there are several M. speciosa chemotypes.
8 citations
TL;DR: N-Protected 3-iodoindoles were reacted with (di)azine halides in a sequentially Pd-catalyzed one-pot fashion, i.e., by Masuda borylation–Suzuki coupling (MBSC) sequence, which successfully applied to the concise syntheses of marine indole alkaloids meridianin C, D, F, and G, as well as to the bisindoles alkaloid scalaridine A.
Abstract: N-Protected 3-iodoindoles were reacted with (di)azine halides in a sequentially Pd-catalyzed one-pot fashion, i.e., by Masuda borylation–Suzuki coupling (MBSC) sequence. This methodology was successfully applied to the concise syntheses of marine indole alkaloids meridianin C, D, F, and G, as well as to the bisindole alkaloid scalaridine A, which were obtained in moderate to excellent yield.
6 citations
TL;DR: Tabernaecorymine A, an 18normonoterpenoid indole alkaloid with conjugated (E)-3-aminoacrylaldehyde fragment was obtained from the stem bark of Tabernaemontana corymbosa as discussed by the authors .
6 citations
TL;DR: It is found that idioblast cells and laticifer cells have different biological roles in MIA biosynthesis and its regulation, and the serpentine content of leaves increased as leaves grew.
5 citations
TL;DR: One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae) as discussed by the authors .
4 citations
TL;DR: One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae) as discussed by the authors.
4 citations
TL;DR: A structurally unprecedented prenylated indole alkaloid, beshanzuamide A (1), together with five known analogues (2, 6) were isolated and identified from the endophytic fungus derived from the needles of the critically endangered conifer Abies beshaneensis as discussed by the authors .
Abstract: A structurally unprecedented prenylated indole alkaloid, beshanzuamide A (1), together with five known analogues (2–6) were isolated and identified from the endophytic fungus derived from the needles of the critically endangered conifer Abies beshanzuensis. The new structure was determined by extensive spectroscopic methods and quantum chemical calculations of NMR and electronic circular dichroism (ECD) data. Compound 1 features a unique N,O-spiroketal/δ-lactone motif connected to a pyranoindole-derived bicyclo[2.2.2]diazaoctane ring. A plausible biogenetic pathway for the assembly of 1 was proposed.
4 citations
TL;DR: In this article , a tetrakis monoterpene indole alkaloid alasmontamine A with a molecular formula of C84 H91 N8 O12 has been calculated at the PBE0/pcSseg-2/pcseg2 level of theory on M06-2X/aug-cc-pVDZ geometry.
Abstract: 1 H and 13 C NMR chemical shifts of a tetrakis monoterpene indole alkaloid alasmontamine A with a molecular formula of C84 H91 N8 O12 have been calculated at the PBE0/pcSseg-2//pcseg-2 level of theory on M06-2X/aug-cc-pVDZ geometry. In the course of the preliminary conformational search, six true minimum energy conformers were identified that can contribute to the actual conformation of this huge alkaloid. Calculated chemical shifts generally demonstrated a good agreement with available experimental data characterized with a corrected mean absolute error of 0.10 ppm for the range of about 7 ppm for protons and 1.1 ppm for the range of about 160 ppm for carbons.
TL;DR: A pair of new diastereoisomers neolignans (1-2) and a new alkaloid (7) were isolated from the stems of Nauclea officinalis as discussed by the authors .
TL;DR: In this article , a method for simultaneous enrichment and separation of vindoline, catharanthine and vinblastine from Catharanthus roseus (Madagascar periwinkle) ionic liquid extracts was developed.
TL;DR: In this paper , a vobasine-tryptamine-based monoterpene indole alkaloid pseudodimer was isolated from the stem bark of Voacanga africana.
Abstract: A new vobasine-tryptamine-based monoterpene indole alkaloid pseudodimer was isolated from the stem bark of Voacanga africana. As a minor constituent occurring in a thoroughly investigated plant, this molecule was targeted based on a molecular networking strategy and a rational MS2-guided phytochemical investigation led to its isolation. Its structure was formally established based on HRMS, 1D/2D NMR data, and the application of the tool Small Molecule Accurate Recognition Technology (SMART 2.0). Its absolute configuration was assigned by the exciton chirality method and TD-DFT ECD calculations. Besides featuring an unprecedented intermonomeric linkage in the small group of vobasine/tryptamine hybrids, pyrrovobasine also represents the first pyrraline-containing representative in the whole monoterpene indole alkaloids group. Biosynthetic hypotheses possibly underpinning these structural oddities are proposed here.
TL;DR: The host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy and the insertion of the indole moiety was confirmed by both techniques.
Abstract: Mitragynine (MTR), the main indole alkaloid of the well-known plant kratom (Mitragyna speciosa), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development. The poor aqueous solubility and low bioavailability of drugs are often improved by cyclodextrins (CyDs) as excipients through host-guest type complex formation. Among the wide variety of CyDs, sulfobutylether-beta-cyclodextrin (SBEβCyD) is frequently used and official in the European and U.S. Pharmacopoeia. Herein, the host-guest complexation of MTR with βCyD and SBEβCyD was studied using chiroptical and NMR spectroscopy. It was found by NMR measurements that MTR forms a rather weak (logβ11 = 0.8) 1:1 host-guest complex with βCyD, while the co-existence of the 2MTR∙SBEβCyD and MTR∙SBEβCyD species was deducted from 1H NMR titrations in the millimolar MTR concentration range. Sulfobutylation of βCyD significantly enhanced the affinity towards MTR. The structure of the formed inclusion complex was extensively studied by circular dichroism spectroscopy and 2D ROESY NMR. The insertion of the indole moiety was confirmed by both techniques.
TL;DR: The metabolism of monoterpene indole alkaloids (MIAs) is an outstanding example of how plants shape chemical diversity from a single precursor.
Abstract: The metabolism of monoterpene indole alkaloids (MIAs) is an outstanding example of how plants shape chemical diversity from a single precursor. Here we report the discovery of novel enzymes from the Alstonia scholaris tree, a cytochrome P450, an NADPH dependent oxidoreductase and a BAHD acyltransferase that together synthesize the indole alkaloid akuammiline with a unique methanoquinolizidine cage structure. The two paralogous cytochrome P450 enzymes rhazimal synthase (AsRHS) and geissoschizine oxidase (AsGO) catalyse the cyclization of the common precursor geissoschizine and they direct the MIA metabolism towards to the two structurally distinct and medicinally important MIA classes of akuammilan and strychnos alkaloids, respectively. To understand the pathway divergence, we investigated the catalytic mechanism of the two P450 enzymes by homology modelling and reciprocal mutations. Upon conducting mutant enzyme assays, we identified a single amino acid residue that mediates the space in active sites, switches the enzymatic reaction outcome and impacts the cyclization regioselectivity. Our results represent a significant advance in MIA metabolism, paving the way for discovery of downstream genes in akuammilan alkaloid biosynthesis and facilitating future synthetic biology applications. We anticipate that our work presents, for the first time, insights at the molecular level for plant P450 catalytic activity with a significant key role in the diversification of alkaloid metabolism, and provides the basis for designing new drugs.
TL;DR: It is expected that access to these resources will facilitate the elucidation of unknown MIA biosynthetic routes with the potential of transferring these pathways to heterologous expression systems for large-scale MIA production.
Abstract: Abstract Vinca minor, also known as the lesser periwinkle, is a well-known species from the Apocynaceae, native to central and southern Europe. This plant synthesizes monoterpene indole alkaloids, which are a class of specialized metabolites displaying a wide range of bioactive- and pharmacologically important properties. Within the almost 50 monoterpene indole alkaloids it produces, V. minor mainly accumulates vincamine, which is commercially used as a nootropic. Using a combination of Oxford Nanopore Technologies long read- and Illumina short-read sequencing, a 679,098 Mb V. minor genome was assembled into 296 scaffolds with an N50 scaffold length of 6 Mb, and encoding 29,624 genes. These genes were functionally annotated and used in a comparative genomic analysis to establish gene families and to investigate gene family expansion and contraction across the phylogenetic tree. Furthermore, homology-based monoterpene indole alkaloid gene predictions together with a metabolic analysis across 4 different V. minor tissue types guided the identification of candidate monoterpene indole alkaloid genes. These candidates were finally used to identify monoterpene indole alkaloid gene clusters, which combined with synteny analysis allowed for the discovery of a functionally validated vincadifformine-16-hydroxylase, reinforcing the potential of this dataset for monoterpene indole alkaloids gene discovery. It is expected that access to these resources will facilitate the elucidation of unknown monoterpene indole alkaloid biosynthetic routes with the potential of transferring these pathways to heterologous expression systems for large-scale monoterpene indole alkaloid production.
TL;DR: In this article , four indole-C-mannopyranoside alkaloids, neopetrosins A-D (1-4), together with one new diamine alkaloid, haliclorensin D (6), were isolated from the marine sponge NeOPetrosia chaliniformis collected off Xisha Island in the South China Sea.
Abstract: Four new indole-C-mannopyranoside alkaloids, neopetrosins A-D (1-4), together with one new diamine alkaloid, haliclorensin D (6), were isolated from the marine sponge Neopetrosia chaliniformis collected off Xisha Island in the South China Sea. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, calculated electronic circular dichroism (ECD), and DP4+ probability analyses. Compounds 1, 2, and 4 exhibited in vivo hepatoprotective activity in a zebrafish model at a concentration of 20 μM.
TL;DR: In this article , ten new indole alkaloids (1, 10, 11, 12, 14, 15, 16, 17, 19, 20, 21 and 21) were isolated from the stems and hooks of Uncaria rhynchophylla and their structure elucidation was based on extensive NMR studies, MS and ECD data.
TL;DR: In this paper , three monoterpenoid indole alkaloids, gelsevietmines-A, B, C (1, 2), were isolated from Gelsemium elegans seeds collected in Vietnam.
TL;DR: In this article , a strategy of utilizing oxidative phenolic coupling reaction and regioselective intramolecular aza-Michael reaction to generate fused polycyclic structural frameworks, and its application to total syntheses of (+)-gracilamine and various hasubanan alkaloids.
Abstract: Alkaloids with fused polycyclic frameworks are attractive targets for synthetic organic chemists because of their structural complexity and biological activities, and a variety of synthetic strategies have been developed. Herein, we describe our strategy of utilizing oxidative phenolic coupling reaction and regioselective intramolecular aza-Michael reaction to generate fused polycyclic structural frameworks, and its application to total syntheses of (+)-gracilamine and various hasubanan alkaloids.
01 Jan 2022
TL;DR: The latest progress in understanding the roles of oxidative enzymes in MIA metabolism is discussed and a bioinformatic and biochemical pipeline to identify, characterize, and make use of these plant biocatalysts is described.
TL;DR: A pentacyclic monoterpenoid indole alkaloid glycoside named secorubenine (1) was isolated from the heartwood of Adina rubescens, collected in Indonesia as discussed by the authors .
Abstract: A new pentacyclic monoterpenoid indole alkaloid glycoside named secorubenine (1) was isolated from the heartwood of Adina rubescens, collected in Indonesia. The structure was elucidated by spectroscopic analysis and chemical modification of isolated secorubenine (1). The bioinspired enantioselective total synthesis of 1 was accomplished in 12 steps, whereafter its structure was determined and the absolute stereochemistry was confirmed.
TL;DR: In this paper , a short time series expression analysis captured 58 pathway genes and 12 hub regulators responsible for Uncaria rhynchophylla (UR) biosynthesis and regulation, which were strong links with main UR-MIA features.
TL;DR: In this paper , three unprecedented indole alkaloids, wincalines A, C, and 4 known ones (4, 7), classified into six carbon skeletal types, were isolated from the leaves of Winchia calophylla.
TL;DR: Taberbufamines A and B possess an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring as discussed by the authors .