Indole Alkaloids Research Articles

Predictable regulation of gut microbiome in immunotherapeutic efficacy of gastric cancer.

Immunotherapy has showcased remarkable progress in the management of gastric cancer (GC), prompting the need to proactively identify and classify patients suitable for immunotherapy. Here, 30 patients were enrolled and stratified into three groups (PR, partial response; SD, stable disease; PD, progressive disease) based on efficacy assessment. 16S rRNA sequencing were performed to analyze the gut microbiome signature of patients at three timepoints. We found that immunotherapy interventions perturbed the gut microbiota of patients. Additionally, although differences at the enterotype level did not distinguish patients' immunotherapy response, we identified 6, 7, and 19 species that were significantly enriched in PR, SD, and PD, respectively. Functional analysis showed that betalain biosynthesis and indole alkaloid biosynthesis were significantly different between the responders and non-responders. Furthermore, machine learning model utilizing only bacterial biomarkers accurately predicted immunotherapy efficacy with an Area Under the Curve (AUC) of 0.941. Notably, Akkermansia muciniphila and Dorea formicigenerans played a significant role in the classification of immunotherapy efficacy. In conclusion, our study reveals that gut microbiome signatures can be utilized as effective biomarkers for predicting the immunotherapy efficacy for GC.

Haploid-Phased Chromosomal Telomere-to-Telomere Genome Assembly of Medicinal Plant Uncaria rhynchophylla Dissects Genetic Controls on the Biosynthesis of Bioactive Alkaloids.

Natural indole alkaloids provide important medicinal resources and defences to environmental stresses. The Uncaria genus is a recorded traditional medicinal woody plant with high alkaloids. Genomic insights into alkaloid variation remain elusive. Here, we have dissected the haploid-resolved chromosomal T2T genome assembly of Uncaria rhynchophylla with a size of ~634 Mb and contig N50 of 27 Mb using PacBio HiFi long-reads plus Hi-C reads and anchored the contigs on 22 pairs of confirmed chromosomes. This genome contains 56% repeat sequences and ~29 000 protein-encoding genes. U. rhynchophylla diverged from a common ancestor shared with Coffea around 20 million years ago and contains expanded and contracted gene families associated with secondary metabolites and defences/resistance to stresses. We constructed the pathway and mined genes for rhynchophylline alkaloid biosynthesis. Fifty-three alkaloids in this pathway and eight differentially expressed genes are the keys to alkaloid accumulation. Elevated alkaloid levels are driven by high copy numbers of critical genes STRs and SGRs involved in strictosidine synthesis and hydrolysis as evidenced by phylogenetic, expression and RNA interference analyses. These results advance our genetic understanding and guide further breeding improvements, stress adaptation studies and pharmaceutical development.

Glycosparvine A, a new indole alkaloid from the leaves of Glycosmis parviflora

In the course of our ongoing search for biologically active compounds from medicinal plant, the ethyl acetate extract from the leaves of Glycosmis parviflora (Rutaceae) was investigated. Six compounds including a new indole alkaloid, glycosparvine A (1), and five previously known metabolites (2–6) were identified. The structure of the new compound (1) was unambiguously elucidated by spectroscopic analyses, including 1D/2D NMR spectroscopy and HRESIMS. The absolute configuration of 1 was assigned by comparing its experimental ECD spectra with those reported for similar compound in the literature. Compounds 3 and 6 exhibited moderate inhibitory effects against acetylcholinesterase (AChE) with IC50 values of 35.1 and 2.8 mM, respectively.

Neuroprotective Effect of Natural Indole and β-carboline Alkaloids against Parkinson's Disease: An Overview.

Parkinson's disease (PD) is a devastating neurodegenerative condition that mostly damages dopaminergic neurons in the substantia nigra and impairs human motor function. Males are more likely than females to have PD. There are two main pathways associated with PD: one involves the misfolding of α-synuclein, which causes neurodegeneration, and the other is the catalytic oxidation of dopamine via MAO-B, which produces hydrogen peroxide that can cause mitochondrial damage. Parkin (PRKN), α-synuclein (SNCA), heat shock protein (HSP), and leucine-rich repeat kinase-2 (LRRK2) are some of the target areas for genetic alterations that cause neurodegeneration in Parkinson's disease (PD). Under the impact of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is also important in Parkinson's disease (PD), inhibition of mitochondrial complex 1 results in enhanced ROS generation in neuronal cells. Natural products are still a superior option in the age of synthetic pharmaceuticals because of their lower toxicity and moderate side effects. A promising treatment for PD has been discovered using beta-carboline (also known as " β-carboline") and indole alkaloids. However, there are not many studies done on this particular topic. In the herbs containing β-carbolines and indoles, the secondary metabolites and alkaloids, β-carbolines and indoles, have shown neuroprotective and cognitive-enhancing properties. In this review, we have presented results from 18 years of research on the effects of indole and β-carboline alkaloids against oxidative stress and MAO inhibition, two key targets in PD. In the SAR analysis, the activity has been correlated with their unique structural characteristics. This study will undoubtedly aid researchers in looking for new PD treatment options.

Cytotoxic monoterpenoid indole alkaloids from Tabernaemontana bovina.

Chemical investigation of the native medicinal plant Tabernaemontana bovina led to the isolation of five previously unreported monoterpenoid indole alkaloids tabernovinaines A-E (1-5) together with twenty-seven known analogs (6-32), including a bisindole alkaloid 1 with the (E)-4-aminobut-3-en-2-one fragment, as well as a unique cage skeleton 2 containing 6/5/8/6/6 ring system. The chemical structures of these unreported compounds were elucidated using mass spectrometry, NMR spectroscopy, circular dichroism, density functional theory calculations, and derivatizations. The activity evaluation shows that the bisindole alkaloid 1 revealed a potential cytotoxic effect by inducing HepG2 cell apoptosis and damaging clonal sphere expansion.

Modulation of Terpenoid Indole Alkaloid Biosynthesis in Catharanthus roseus by Sphingomonas Sp Y503 via the CrMAPKKK1-CrMAPKK1/CrMAPKK2-CrMPK3 Signaling Cascade.

Catharanthus roseus is a highly relevant model for investigating plant defense mechanisms and the biosynthesis of therapeutically valuable compounds, including terpenoid indole alkaloids (TIAs). It has been demonstrated that beneficial microbial interactions can regulate TIA biosynthesis in C. roseus, highlighting the need to fully comprehend the molecular mechanisms involved to efficiently implement eco-friendly strategies. This study explores the effects of a novel microbial strain, Y503, identified as Sphingomonas sp., on TIA production and the underlying mechanisms in C. roseus. Through bioinformatics analysis, we have identified 17 MAPKKKs, 7 MAPKKs, and 13 MAPKs within the C. roseus genome. Further investigation has verified the presence of the MAPK module (CrMAPKKK1-CrMAPKK1/CrMAPKK2-CrMPK3) mediating Y503 in regulating TIA biosynthesis in C. roseus. This study provides foundational information for strengthening the plant defense system in C. roseus through advantageous microbial interactions, which could contribute to the sustainable cultivation of medicinal plants such as C. roseus.

Cell-type-aware regulatory landscapes governing monoterpene indole alkaloid biosynthesis in the medicinal plant Catharanthus roseus.

In plants, the biosynthetic pathways of some specialized metabolites are partitioned into specialized or rare cell types, as exemplified by the monoterpenoid indole alkaloid (MIA) pathway of Catharanthus roseus (Madagascar Periwinkle), the source of the anticancer compounds vinblastine and vincristine. In the leaf, the C. roseus MIA biosynthetic pathway is partitioned into three cell types with the final known steps of the pathway expressed in the rare cell type termed idioblast. How cell-type specificity of MIA biosynthesis is achieved is poorly understood. We generated single-cell multi-omics data from C. roseus leaves. Integrating gene expression and chromatin accessibility profiles across single cells, as well as transcription factor (TF)-binding site profiles, we constructed a cell-type-aware gene regulatory network for MIA biosynthesis. We showcased cell-type-specific TFs as well as cell-type-specific cis-regulatory elements. Using motif enrichment analysis, co-expression across cell types, and functional validation approaches, we discovered a novel idioblast-specific TF (Idioblast MYB1, CrIDM1) that activates expression of late-stage MIA biosynthetic genes in the idioblast. These analyses not only led to the discovery of the first documented cell-type-specific TF that regulates the expression of two idioblast-specific biosynthetic genes within an idioblast metabolic regulon but also provides insights into cell-type-specific metabolic regulation.

Evaluation of Vincamine Loaded with Silver Nanoparticles as a New Potential Therapeutic Agent Against Ehrlich's Solid Carcinoma in Mice.

Vincamine, a monoterpenoid indole alkaloid with vasodilatory properties, is extracted from the leaves of Vinca minor. The present study aimed to determine the potential anticancer effects of vincamine loaded in silver nanoparticles (VCN-AgNPs) in mice with Ehrlich solid carcinoma (ESC). After tumor transplantation, the mice were divided into five groups: ESC, ESC+Cisplatin (CPN; 5 mg/kg), ESC+VCN (40 mg/kg), ESC+AgNPs (6 mg/kg), and ESC+VCN-AgNPs (20 mg/kg). The administration of VCN-AgNPs to ESC-bearing mice improved their survival rate and reduced their body weight, tumor size, and tumor weight compared to the ESC group. Furthermore, VCN-AgNPs intensified oxidative stress in tumor tissues, as evidenced by elevated levels of lipid peroxidation (LPO) and nitric oxide (NO), along with a reduction in the levels of the antioxidants investigated (GSH, GPx, GR, SOD, CAT, and TAC). Furthermore, VCN-AgNPs increased the apoptotic proteins Bax and caspase-3, decreased the anti-apoptotic protein (Bcl-2), increased the inflammatory markers TNF-α and IL-1β, and inhibited angiogenesis by lowering VEGF levels in tumor tissues, all of which led to apoptosis. Furthermore, histopathological studies showed that VCN-AgNPs suppressed the progression of Ehrlich carcinoma and induced the formation of clusters of necrotic and fragmented tumor cells. VCN-AgNPs possess cytotoxic and genotoxic effects against ESC because of their pro-oxidant, pro-apoptotic, pro-inflammatory, and antiangiogenic effects. Additionally, the combination of VCN-AgNPs was more effective and safer than chemically synthesized AgNPs, as indicated by an increase in the lifespan of animals and the total tumor inhibition index.

Computation‐Guided Scope Exploration of a Conjugate Addition/Truce‐Smiles Cascade Reaction for Scaffold Diversification

Based on the successful application of a nitroaryl transfer cascade reaction in the total synthesis of various monoterpene indole alkaloids proceeding via fused bicyclic intermediate, we investigated analogous cascade reactions involving spiro, bridged, and alternatively fused bicyclic intermediates. Unfortunately, none of these was found to afford the desired nitroaryl transfer product. DFT studies of the original cascade process revealed that the Truce‐Smiles rearrangement is the rate‐determining step. In addition, we found that the subsequent SO2 extrusion is accompanied by retro‐Mannich ring opening, resulting in a stabilized enolate that only recyclizes after activation of the cyclic imine moiety. Computation of the reaction profiles of the proposed alternative cascade reactions showed that the barrier for the Truce‐Smiles rearrangement is unreasonably high for the bridged and alternatively fused systems, but only moderately higher for the five‐membered spiro system. Reasoning that even more electron‐deficient arenesulfonamides should have a lower barrier for the Truce‐Smiles rearrangement, we synthesized the corresponding 2,4‐dinitrobenzenesulfonamide precursor and found that it indeed smoothly undergoes the nitroaryl transfer cascade at room temperature. In this case, however, the cascade reaction produces a cyclic imine product, as the intermediate 2,4‐dinitrophenyl‐substituted enolate is insufficiently nucleophilic to undergo the Mannich cyclization.

Genome-based discovery of pachysiphine synthases in Tabernaemontana elegans.

Plant-specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti-Alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine-related MIAs in planta remains scarce, limiting the prospects for the biotechnological supply of many pachysiphine-derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlight the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor-made synthesis of non-natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine-derived drugs by microbial cell factories.

Investigation on taxonomy, secondary metabolites and antibacterial activity of Streptomyces sediminicola sp. nov., a novel marine sediment-derived Actinobacteria.

Marine actinomycetes, especially Streptomyces, are recognized as excellent producers of diverse and bioactive secondary metabolites on account of the multiplicity of marine habitations and unique ecological conditions, which are yet to be explored in terms of taxonomy, ecology, and functional activity. Isolation, culture and genome analysis of novel species of Streptomyces to explore their potential for discovering bioactive compounds is an important approach in natural product research. A marine actinobacteria, designated strain SCSIO 75703T, was isolated, and the potential for bioactive natural product discovery was evaluated based on genome mining, compound detection, and antimicrobial activity assays. The phylogenetic, phenotypic and chemotaxonomic analyses indicate that strain SCSIO 75703T represents a novel species in genus Streptomyces, for which the name Streptomyces sediminicola sp. nov. is proposed. Genome analysis revealed the presence of 25 secondary metabolite biosynthetic gene clusters. The screening for antibacterial activity reveals the potential to produce bioactive metabolites, highlighting its value for in-depth exploration of chemical constituents. Seven compounds (1-7) were separated from the fractions guided by antibacterial activities, including three indole alkaloids (1-3), three polyketide derivatives (4-6), and 4-(dimethylamino)benzoic acid (7). These primarily antibacterial components were identified as anthracimycin (4), 2-epi-anthracimycin (5) and β-rubromycin (6), presenting strong antibacterial activities against Gram-positive bacteria with the MIC value ranged from 0.125 to 16μg/mL. Additionally,, monaprenylindole A (1) and 3-cyanomethyl-6-prenylindole (2) displayed moderate inhibitory activities against α-glucosidase with the IC50 values of 83.27 and 86.21μg/mL, respectively. Strain SCSIO 75703T was isolated from marine sediment and identified as a novel species within the genus Streptomyces. Based on genomic analysis, compounds isolation and bioactivity studies, seven compounds were identified, with anthracimycin and β-rubromycin showing significant biological activity and promising potential for further applications.

Rational Design and Stereodivergent Construction of Enantioenriched Tetrahydro-β-Carbolines Containing Multistereogenic Centers.

Chiral tetrahydro-β-carbolines, as one of the most intriguing subtypes of indole alkaloids, have emerged as the privileged units in plenty of natural products and biologically active molecules with an impressive range of bioactive properties. However, the stereodivergent construction of these valuable skeletons containing multistereogenic centers from readily available starting materials remains very challenging, especially, in view of the introduction of an axial chirality. Herein, we developed an efficient method toward enantioenriched tetrahydro-β-carbolines with readily available tryptophan-derived aldimine esters and allylic carbonates under mild reaction conditions. The reaction proceeds in a sequential fashion involving synergistic Cu/Ir-catalyzed stereodivergent allylation and the Brønsted acid-promoted stereospecific Pictet-Spengler reaction, affording a wide range of chiral tetrahydro-β-carbolines bearing up to four stereogenic centers in good yields with excellent stereoselectivity control. When N-aryl-substituted tryptophan-derived aldimine esters were utilized, notably, a unique C-N heterobiaryl axis could be simultaneously constructed with the formation of the third point stereogenic center in the last cyclization step through dynamic kinetic resolution (DKR). Computational mechanistic studies established a plausible synergistic mechanism for dual Cu/Ir-catalyzed asymmetric allylation and the succeeding protonation-assisted Pictet-Spengler cyclization to complete the annulation. Structure-activity relationship analyses unveil the origins of stereochemistry for the building of one axis and three point stereogenic centers.

Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

Polyketide Origin of the Indole Ring during the Biosynthesis of Indole Alkaloid Coprisidins.

Coprisidins, a new class of indole alkaloids, feature a 1,4-naphthoquinone moiety attached to C-3 of 2-oxindole. Heterologous expression of a type II polyketide synthase-containing gene cluster resulted in the generation of three coprisidins. Gene disruption and isotope feeding studies suggested that the 2-oxindole moieties of coprisidins originate from a tetracyclic aromatic polyketide through oxidative rearrangements. This represents a novel biosynthetic route for the synthesis of indole rings in nature.

Cardioprotective effect of Perakine against myocardial ischemia-reperfusion injury of type-2 diabetic rat in Langendorff-Perfused Rat Hearts: Role of TLR4/NF-kB signalling pathway.

Myocardial ischemia-reperfusion (I/R) injury is a grave life-threatening situation, if not treated well in time. The development of natural remedies for myocardial I/R injury has witnessed dramatic growth in the last decade. Prompted by the above, in the present study, we have elucidated the pharmacological effect of Perakine (PER), an indole alkaloid in myocardial ischemia-reperfusion injury in type 2 diabetic rats. The model was established by inducing diabetes in experimental rats followed by the development of myocardial I/R injury model of isolated rat heart by the use of improved Langendorff retrograde perfusion technology. Results of the study suggest that PER significantly lowered the infarct size and infarct volume, and improvement in cardiac ability (LVSP, ±dP/dtmax, and heart rate). It also showed a significant lowering of cardiac biomarkers (CK, CK(MB), ALT, AST, and LDH) in a dose-dependent manner as compared to unprotected IR rats. The level of oxidative stress (MDA, SOD, and GSH) was also found lowered in IR rats together with a reduction in the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α). The anti-inflammatory acting of PER on IR rats is believed to be linked with the reduction of TNF-α, NF-κB, and TLR4 in both RT-qPCR and western blot analysis. Our research showed that Perakine could potentially alleviate cardiac ischemia-reperfusion injury in rats by blocking the TLR4/NF-κB signaling cascade.

Binding characteristics of the major kratom alkaloid, mitragynine, towards serum albumin: Spectroscopic, calorimetric, microscopic, and computational investigations

Mitragynine (MTG) is a prominent indole alkaloid that is present abundantly in Mitragyna speciosa, commonly referred to as kratom. MTG has garnered significant attention due to its selective agonistic characteristics towards opioid receptors and related analgesic effects. In the circulatory system, the in vivo efficacy of MTG is dictated by its interaction with plasma proteins, primarily human serum albumin (HSA). In the present study, we utilized a broad methodology that included spectroscopic, calorimetric, microscopic, and in silico approaches to characterize the interaction between MTG and HSA. Alterations in the UV absorption spectrum of HSA by the presence of MTG demonstrated a ground-state complexation between the protein and the ligand. The Ka values obtained for the MTG–HSA interaction were in the range 103–104 M−1 based on analysis of fluorescence and ITC data, respectively, indicating an intermediate binding affinity. The binding reaction was thermodynamically favorable as revealed by ΔH, ΔS, and ΔG values of −16.42 kJ mol−1, 39.97 J mol−1 K−1, and −28.34 kJ mol−1, respectively. Furthermore, CD spectroscopy results suggested MTG binding induced minimal effects on the structural integrity of HSA, supported by computational methods. Changes in the dimensions of HSA particles due to aggregation, as observed using atomic force microscopy in the presence of MTG. Competitive drug displacement results seemingly suggested site III of HSA located at subdomain IB as the preferred binding site of MTG, but were in inconclusive. However, docking results showed the clear preference of MTG to bind to site III, facilitated by hydrophobic (alkyl and pi-alkyl) and van der Waals forces, together with carbon hydrogen bonds. Additionally, the MTG–HSA complexation was demonstrated to be stable based on molecular dynamics analysis. The outcomes of this study shed light on the therapeutic potential of MTG and can help in the design of more effective derivatives of the compound.

Salivary microbiota composition before and after use of proton pump inhibitors in patients with laryngopharyngeal reflux: a self-control study

BackgroundIssues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study.MethodsThirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results.ResultsThe alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R2 = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter_gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples ( P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050).ConclusionsThese findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients.Chinese clinical trial registryNo. ChiCTR2300067507. Registered on January 10,2023 retrospectively.Level of evidence4.

Evaluating of effects for the sequence fermentation with M. pulcherrima and I. terricola on mulberry wine fermentation: Physicochemical, flavonoids, and volatiles profiles

This study investigates the variation of physicochemical, flavonoids, and volatiles during sequential fermentation which Metschnikowia pulcherrima and Issatchenkia terricola as sequential co-fermenters and a single fermentation by Saccharomyces cerevisiae in mulberry wine. Sequential fermentation shown that β-glucosidase activity greater and fermentation time declined to 144 h. In addition, 11 flavonoids (apigenin-5-O-glucoside, aromadendrin-7-O-glucoside, kaempferol-3,7-O-diglucoside, and so on) were significantly increased. Significant differences were found between types of metabolic products enriched in flavone and flavonol biosynthesis and anthocyanins biosynthesis, with an enrichment ratio of 46.15 % and 23.08 %, respectively. 16 apple-scented compounds (2-Buten-1-one, (E)-1-(2,6,6-trimethyl-1,3-cyclohexadien-1-yl)-, Butanoic acid, (Z)-3-hexenyl ester, 3-methyl-1-methylethyl-Butanoic acid ester, and so on), 5 rose-scented (e.g. benzyl alcohol, ethyl geranate, hydrocinnamic acid), and 4 balsamic-scented compounds ((−)-myrtenol, benzoic acid 1-methylethyl ester, benzyl alcohol, p-cymen-7-ol) were distinctively present. Interestingly, tryptophan metabolism and indole alkaloid biosynthesis are only enriched in sequential fermentation.

Unveiling the impact of nitrogen deficiency on alkaloid synthesis in konjac corms (Amorphophallus muelleri Blume)

BackgroundKonjac corms are known for their alkaloid content, which possesses pharmacological properties. In the primary cultivation areas of konjac, nitrogen deficiency is a common problem that significantly influences alkaloid synthesis. The impact of nitrogen deficiency on the alkaloids in konjac corms remains unclear, further complicated by the transition from mother to daughter corms during their growth cycle.ResultsThis study examined 21 alkaloids, including eight indole alkaloids, five isoquinoline alkaloids, and eight other types of alkaloids, along with the associated gene expressions throughout the development of Amorphophallus muelleri Blume under varying nitrogen levels. Nitrogen deficiency significantly reduced corm diameter and fresh weight and delayed the transformation process. Under low nitrogen conditions, the content of indole alkaloids and the expression of genes involved in their biosynthesis, such as tryptophan synthase (TRP) and tryptophan decarboxylase (TDC), exhibited a substantial increase in daughter corms, with fold changes of 61.99 and 19.31, respectively. Conversely, in the mother corm, TDC expression was markedly reduced, showing only 0.04 times the expression level observed under 10 N treatment. The patterns of isoquinoline alkaloid accumulation in corms subjected to nitrogen deficiency were notably distinct from those observed for indole alkaloids. The accumulation of isoquinoline alkaloids was significantly higher in mother corms, with expression levels of aspartate aminotransferase (GOT), chorismate mutase (CM), tyrosine aminotransferase (TAT), and pyruvate decarboxylase (PD) being 4.30, 2.89, 921.18, and 191.40 times greater, respectively. Conversely, in daughter corms, the expression levels of GOT and CM in the 0 N treatment were markedly lower (0.01 and 0.83, respectively) compared to the 10 N treatment.ConclusionsThe study suggests that under nitrogen deficiency, daughter corms preferentially convert chorismate into tryptophan to synthesize indole alkaloids, while mother corms convert it into tyrosine, boosting the production of isoquinoline alkaloids. This research provides valuable insights into the mechanisms of alkaloid biosynthesis in A. muelleri and can aid in developing nitrogen fertilization strategies and in the extraction and utilization of alkaloids.

3-Acetyl Indole in the Synthesis of Natural Bioactive Compounds

Natural products, with their various sources from plants, marine organisms, and microorganisms, are considered a key source and inspiration for medicines and continue to be so. Indole alkaloids are a class of alkaloids and represent a large subunit of natural prod-ucts. Indole alkaloids of biological importance are numerous and cover a wide range of phar-maceutical applications, including anticancer, antiviral, antimicrobial, anti-inflammatory, and antioxidant. Obtaining natural, biologically active indole compounds involves isolating them from their natural sources or preparing them synthetically. 3-Substituted indoles repre-sent an emerging structural class of marine alkaloids based on their high degree of biological activity. 3-Acetyl indole is an important core used as a starting material for synthesizing many bioactive indole alkaloids. (5-Indole)oxazole alkaloids, β-carboline alkaloids, bis-in-dole alkaloids, chuangxinmycin, meridianine, and (±) indolemycin are the most important indole alkaloids that are prepared starting from 3-acety indole. The present review provides comprehensive information on the structures and the synthesis of bioactive indole alkaloids utilizing 3-acetyl indole and its derivatives as starting compounds. Additionally, it also spot-lights the diverse biological activities of these compounds.