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Indole, a versatile outstanding heterocyclic compound, engaged in numerous pharmacological properties due to their multiple biochemical processes. The remarkable indole moiety resembles with numerous protein structures. The fascinating molecular framework of indole makes its suitable for drug development. Indole derivatives mimic the peptides structure and bind reversibly to several enzymes, which contribute enormous opportunities to develop novel drugs with distinct mechanism of action Indole, a versatile outstanding heterocyclic compound, engaged in numerous pharmacological properties due to their multiple biochemical processes. The remarkable indole moiety resembles with numerous protein structures. The fascinating molecular framework of indole makes its suitable for drug development. Indole derivatives mimic the peptides structure and bind reversibly to several enzymes, which contribute enormous opportunities to develop novel drugs with distinct mechanism of actionIndole, a versatile outstanding heterocyclic compound, engaged in numerous pharmacological properties due to their multiple biochemical processes. The remarkable indole moiety resembles with numerous protein structures. The fascinating molecular framework of indole makes its suitable for drug development. Indole derivatives mimic the peptides structure and bind reversibly to several enzymes, which contribute enormous opportunities to develop novel drugs with distinct mechanism of actionIndole, a versatile outstanding heterocyclic compound, engaged in numerous pharmacological properties due to their multiple biochemical processes. The remarkable indole moiety resembles with numerous protein structures. The fascinating molecular framework of indole makes its suitable for drug development. Indole derivatives mimic the peptides structure and bind reversibly to several enzymes, which contribute enormous opportunities to develop novel drugs with distinct mechanism of action In the present work, synthesis and biological activity of new indole based derivatives as potent anti-inflammatory agent. The derivatives were schemed and substituted, they were checked for docking scores against the Cyclooxygenase II enzyme. From that 10 best docked compounds are selected and synthesized spectral data of the synthesized compounds was obtained from IR, 1HNMR, 13CNMR, and mass spectroscopy, among the tested compounds. From the docking results, compound A7 and A10 (9.2 Kcal/mol) shows the highest binding affinity against Cyclooxygenase II enzyme possesses anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Unleashing prodrugs through nitro-reduction is a promising strategy in cancer treatment. In this study, we present a unique bioorthogonal reaction for aromatic nitro reduction, mediated by 4,4'-bipyridine. The reaction is a rare example of organocatalyst-mediated bioorthogonal reaction. This bioorthogonal reaction demonstrates broad substrate scope and proceeds at low micromolar concentrations under biocompatible conditions. Our mechanistic study reveals that water is essential for the reaction to proceed at biorelevant substrate concentrations. We illustrate the utility of our reaction for controlled prodrug activation in mammalian cells, bacteria, and mouse models. Furthermore, a nitro-reduction-annulation cascade is developed for the synthesis of indole derivatives in living cells. Releasing prodrugs through nitroreduction is a promising strategy in cancer treatment. In this study, the authors present a 4,4'-bipyridine-mediated bioorthogonal aromatic nitro reduction for activation of nitro prodrugs. [ABSTRACT FROM AUTHOR]

Indole derivatives have become an important class of compounds in medicinal chemistry, recognized for their wide-ranging biological activities and therapeutic potential. This review provides a comprehensive overview of recent advances in the evaluation of indole-based compounds in the last five years, highlighting their roles in cancer treatment, infectious disease management, anti-inflammatory therapies, metabolic disorder interventions, and neurodegenerative disease management. Indole derivatives have shown significant efficacy in targeting diverse biological pathways, making them valuable scaffolds in designing new drugs. Notably, these compounds have demonstrated the ability to combat drug-resistant cancer cells and pathogens, a significant breakthrough in the field, and offer promising therapeutic options for chronic diseases such as diabetes and hypertension. By summarizing recent key findings and exploring the underlying biological mechanisms, this review underscores the potential of indole derivatives in addressing major healthcare challenges, thereby instilling hope and optimism in the field of modern medicine. [ABSTRACT FROM AUTHOR]

In the present work, the indole derivative, namely, 3,3′,3″-methane-triyl-tris-1H-indol (tris-Ind), is synthesized and characterized as an organic electrode material in rechargeable lithium-ion batteries (RLIB). The structural characterization of the synthesized molecule is carried out using physicochemical techniques. The ball milling method is used for the lithiation process to form electroactive lithiated tris-Ind (Li-tris-Ind). The electrochemical activity of Li-tris-Ind is measured in aqueous and non-aqueous electrolytic media, and the results are compared. The aqueous cell system delivers an average cell potential of 0.76 V with a discharge capacity of 189 mAhg−1, whereas the non-aqueous cell system delivers an average potential of 1 V with 506 mAhg−1. The potentiostatic electrochemical impedance spectroscopic studies reveal the kinetics of finite diffusion. The organic electrode shows good cyclic stability and reproducibility in both systems, making it a significant practical material for RLIB applications. [ABSTRACT FROM AUTHOR]

In this study, we synthesized a variety of indole derivatives using commercially available 2,5‐dimethoxybenzaldehyde 18 as a starting material. The synthetic route involves a sequential usage of Knoevenagel and Fischer indolization reactions as key steps and the Fischer indolization is facilitated by deep eutectic solvent (DES) such as L‐tartaric acid/dimethylurea (TA:DMU). All the compounds prepared here are characterized by HRMS, 1H‐NMR and 13C‐NMR data. The methodology described in this study showcases the utility of deep eutectic solvents in facilitating the synthesis of diverse indole derivatives, thereby expanding the toolkit of sustainable synthetic methodologies. These compounds are medicinally important and play a key role as an effective template in Kinase inhibitors (CK2). Various functionalized indeno[1,2‐b]indole scaffolds synthesized here might be valuable as novel inhibitors of human CK2. Elevated levels of protein kinase CK2, previously known as casein kinase 2 or II, have been linked to higher cell growth and proliferation in both normal and cancerous cells. [ABSTRACT FROM AUTHOR]

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logPTLC) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logPTLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds. [ABSTRACT FROM AUTHOR]

We described a copper(I)‐catalyzed atom economic and selective hydroamination‐cyclization of alkynyl‐tethered quinazolinones to prepare a variety of indole‐fused pyrazino[1,2‐a]quinazolinones in good to excellent yields ranging from 39 %–99 % under mild reaction conditions. Control experiments revealed that coordination‐directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination‐cyclization of alkynes at the N1‐atom instead of N3‐atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole‐fused pyrazino[1,2‐a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions. [ABSTRACT FROM AUTHOR]

Bacterial therapy for colorectal cancer (CRC) represents a burgeoning frontier. The probiotic Limosilactobacillus fermentum GR-3, derived from traditional food "Jiangshui", exhibited superior antioxidant capacity by producing indole derivatives ICA and IPA. In an AOM/DSS-induced CRC mouse model, GR-3 treatment alleviated weight loss, colon shortening, rectal bleeding and intestinal barrier disruption by reducing oxidative stress and inflammation. GR-3 colonization in distant colon induced apoptosis and reduced tumor incidence by 51.2%, outperforming the control strain and vitamin C. The beneficial effect of GR-3 on CRC was associated with gut microbiome modulation, increasing SCFA producer Lachnospiraceae NK4A136 group and suppressing pro-inflammatory strain Bacteroides. Metagenomic and metabolic analyses revealed that GR-3 intervention upregulated antioxidant genes (xseA, ALDH) and butyrate synthesis gene (bcd), while increasing beneficial metabolites (SCFAs, ICA, IPA, VB12 and VD3) and reducing harmful secondary bile acids. Overall, GR-3 emerges as a promising candidate in CRC therapy, offering effective gut microbiome remediation. [ABSTRACT FROM AUTHOR]

Indoles are common motifs in functional agricultural and pharmaceutical molecules. Heteroatom alkylation is the most frequently used chemical reaction in the pharmaceutical field. Developing protocols for the nucleophilic substitution of (indol-2-yl)methyl electrophiles is important for functionalizing indoles. There are few studies on the nucleophilic substitution at the 2′-position of the electrophiles without an electron-withdrawing group at the 1-position or substituents at the 2′- and 3-positions, where the existing approaches require high temperatures and long reaction times. In this study, we demonstrated rapid (7–12 s) and mild (25 °C) microflow nucleophilic substitution at the 2′-position of indole derivatives without an electron-withdrawing group at the 1-position and substituents at the 2′- or 3-positions. Comparable batch conditions resulted in a lower yield. [ABSTRACT FROM AUTHOR]

The indole scaffold is considered a privileged framework in the design and synthesis of several active pharmaceutical ingredients, particularly as promising anticancer agents. Its presence in several bioactive natural compounds has caught the attention of the scientific community, which has been committed to unveiling its biosynthetic pathways and generating multiple derivatives with innovative synthetic routes. The large variety of structural derivatives enhances their use in multiple bioapplications and pharmacological activities. In this review, the reader will have easy access to some examples of natural and synthetic indole derivatives with antimicrobial, antidepressant, anti-inflammatory, antiviral, antimigraine, and antiemetic activity. However, the main topic of this review is related to cancer and the importance of indole derivatives as promising anticancer drugs. Two of the reasons why cancer is considered a massive problem worldwide are attributed to the struggle to develop target-specific drugs while avoiding drug resistance. Among countless drugs targeting specific proteins involved in tumorigenesis, prompting life quality in the treatment of several cancer types, protein kinases, desoxyribonucleic acid topoisomerases, and P-glycoprotein have been shown to be the main targets when it comes to the development of novel anticancer agents. Furthermore, indole and its derivatives are also studied regarding affinity to other targets related to cancer. This review aims to highlight the utility of the indole scaffold in anticancer drug design, inspiring the creation and synthesis of new derivatives that target specific proteins and address drug resistance challenges. [ABSTRACT FROM AUTHOR]

Indole derivatives are key components of natural products and possess a wide range of biological and pharmaceutical applications. Here, we present the synthesis of a new indole derivative, namely 2-(1-ethyl-5-nitro-1H-indole-7-carbonyl)butyl 4-methylbenzenesulfonate. The structural elucidation of this compound was accomplished through comprehensive spectroscopic analysis, including Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Our molecular docking study revealed that this compound exhibits strong affinity towards tyrosinase, making it a promising candidate as an antioxidant agent. [ABSTRACT FROM AUTHOR]

Tryptophan is one of the essential amino acids in the human body, metabolized to produce indole derivatives such as kynurenine, serotonin, melatonin, and indole-3-acetic acid. It plays a crucial regulatory role in physiological functions. This article uses personification to narrate the story of tryptophan being converted into various products through metabolism and artificial synthesis, highlighting the importance of tryptophan metabolic pathways in diverse life activities. [ABSTRACT FROM AUTHOR]

A series of 1-carbonyl-1H-indoles were prepared by 2-iodoanilines and calcium carbide in a one-pot reaction catalyzed by recyclable10% Pb/C, resulting in the corresponding substituted indoles in good yields. This protocol offers several advantages, including the utilization of sustainable, low-cost calcium carbide, an easy-to-handle acetylene source, and recyclable Pb/C catalysts. The synthesis of a series of 1-carbonyl-1H-indoles were prepared by 2-iodoanilines and calcium carbide in a one-pot reaction catalyzed by 10% Pb/C, resulting in the corresponding substituted indoles in good yields. This protocol offers several advantages, including the utilization of sustainable, low-cost feedstock, an easy-to-handle acetylene source, and recyclable Pb/C catalysts. [ABSTRACT FROM AUTHOR]

The corrosion inhibition activity of indole derivatives has been systematically examined by calculating quantum chemical parameters including energy of the highest occupied molecular orbital, energy of the lowest unoccupied molecular orbital, energy difference, molecular hardness, molecular softness, and the number of electrons exchanged between the metal and the corrosion inhibitor at the B3LYP/6-311++G (d,p) level of theory. The results demonstrate that derivatives containing the electron-donating groups exhibit superior efficiency in inhibiting iron corrosion compared to indole. Additionally, an investigation into the corrosion inhibition ability of derivatives containing the NH2 group reveals that 6-NH2-indole emerges as the most effective inhibitor, boasting an efficiency value of 97.11%. These calculated outcomes align with previously studied experimental results, underscoring the remarkable corrosion resistance of derivatives containing electron-donating groups.

A highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[b]indoles and 6,7-dihydrodibenzo- [a,c][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives. [ABSTRACT FROM AUTHOR]

A series of ethyl 2-[(1H-indol-3-yl)(phenyl)methyl]-3-oxobutanoate derivatives was synthesized via a one-pot multicomponent approach using substituted indoles, ethyl 3-oxobutanoate, and aromatic aldehydes under a conventional heating. The NiO nanoparticles used as nanocatalysts for the Knoevenagel condensation and synthesis of new indole derivatives were discussed. The XRD was used to determine the particle size of the NiO nanoparticle. NiO nanoparticles can be recycled and used again after the reaction course. The ADM analysis and drug-likeness results showed that indole derivatives satisfied the criteria for drug-likeness and Lipinski's principles. The reactivity indices and potential regions derived from the FMO investigations were effectively used in various molecular systems because they offer valuable information. The oxobutanoate derivative's potential reactivity directions were determined and the important areas were highlighted. [ABSTRACT FROM AUTHOR]

Creating a diverse dipolar microenvironment around the active site is of great significance for the targeted induction of intermediate behaviors to achieve complicated chemical transformations. Herein, an efficient and general strategy is reported to construct hypercross‐linked polymers (HCPs) equipped with tunable dipolar microenvironments by knitting arene monomers together with dipolar functional groups into porous network skeletons. Benefiting from the electron beam irradiation modification technique, the catalytic sites are anchored in an efficient way in the vicinity of the microenvironment, which effectively facilitates the processing of the reactants delivered to the catalytic sites. By varying the composition of the microenvironment scaffold structure, the contact and interaction behavior with the reaction participants can be tuned, thereby affecting the catalytic activity and selectivity. As a result, the framework catalysts produced in this way exhibit excellent catalytic performance in the synthesis of glycinate esters and indole derivatives. This manipulation is reminiscent of enzymatic catalysis, which adjusts the internal polarity environment and controls the output of products by altering the scaffold structure. [ABSTRACT FROM AUTHOR]

An alternative approach to synthesize bis‐indolylmethanes (BIMs) via a unique p‐toluenesulfonic acid (PTSA) catalyzed dual Csp3−Csp2 bond‐breaking reaction has been reported here. In the reported protocol, 1,3,5‐trimethoxybenzene (TMB), an electron‐rich and sterically bulky arene, acts as a carbon‐based leaving group which can be recovered after the completion of the reaction. In this process, several BIMs of various indole derivatives can be synthesized from symmetrical triarylmethanes (TRAMs) containing bis‐TMB motifs. By modifying the reaction conditions, we could control the sequential bond cleavage of two Csp3−Csp2 bonds in starting TRAM. [ABSTRACT FROM AUTHOR]

We herein reported, a visible‐light‐induced K2S2O8 mediated cascade reaction of 3‐(2‐isocyanoethyl)indoles with α‐oxocarboxylic acids leading to diastereoselective synthesis of polycyclic spiroindolines bearing an N‐formyl unit derivative utilising the alkali metal salt K2S2O8 as a mediator under mild reaction conditions. This study offers an illustration of α‐oxocarboxylic acids and 3‐(2‐isocyanoethyl)indoles‐based reactions as it shows the involvement of glyoxolate ions without decarboxylation to access polycyclic spiroindolines bearing an N‐formyl unit analogue. The batch process can be extended to a continuous flow system using a glass tube loaded with K2S2O8 placed between the PFA capillary reactor, which can greatly advance the reaction efficiency and can even be promoted to gram‐scale synthesis. [ABSTRACT FROM AUTHOR]

Soybean meal and its processing products have been widely used in fish feeds. In aquaculture, there is a lack of effective targeted protection against food-borne enteritis caused by feeding soybean meal. Our preliminary research found that Indole-3-butyric acid (IBA) has the potential application value. The present research evaluated the influence of supplementing different levels of IBA to diets containing high soybean meal on juvenile pearl gentian grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂). The feeding experiment lasted for eight weeks and the initial weight of the fish was 21.17 ± 0.02 g. The FM diet with fish meal as the main protein source was prepared. In addition, six diets were prepared in which soybean meal was used to replace some of the fish meal as a secondary protein source. IBA was added to these six diets at 0 g/kg, 0.8 g/kg, 1.6 g/kg, 2.4 g/kg, 3.2 g/kg, and 4.0 g/kg respectively. The growth performance of the 2.4 g/kg IBA-added group was significantly higher than that of the non-added group (P < 0.05); the group with IBA additions equal to or more than 2.4 g/kg had longer intestinal folds and more absorptive cells; the levels of ACP, LYS, C3, and C4 in the gut showed a significant quadratic trend of decreasing and then increasing with the increase of IBA and reached a minimum at 2.4 g/kg (P < 0.05); the gene expression of cytokines il1β, il17, tnfα, il4, il5, and tgfβ1 varied significantly among the groups with different IBA additions (P < 0.05). In addition, this study investigated the role of feeding 2.4 g/kg IBA on fish from the perspective of intestinal flora. In this study, we concluded that 2.4 g/kg IBA could be added to diets using soybean meal replacing 40% of fish meal, which had beneficial effects on growth performance, intestinal inflammation alleviation and intestinal flora homeostasis. This provides a theoretical basis for IBA to mitigate SBMIE in pearl gentian grouper and promote the further application of soybean meal in carnivorous fish. [ABSTRACT FROM AUTHOR]

Free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS) cause cellular damage and contribute to thromboembolic diseases by promoting platelet activation and aggregation. Compounds that scavenge free radicals can reduce oxidative stress, decreasing platelet aggregation and thrombus formation. Despite their beneficial biological activities, indoles have clinical limitations due to poor bioavailability, solubility, rapid metabolism, and limited membrane permeability. We designed a new class of indole derivatives (10a–j) with a triazole linker and various amino acids to overcome these issues. These conjugates enhance solubility and bioavailability and possess antioxidant properties. Compounds 10f, 10g, and 10h showed improved permeability and significant anti-platelet aggregation effects, comparable to aspirin. These findings highlight the potential of these new indole derivatives as effective antithrombotic agents, warranting further exploration of their mechanisms and therapeutic applications. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of microbiota-derived indole metabolites towards kynurenine production. Under HFD, the specific deletion of IDO in intestinal epithelial cells leads to intestinal inflammation, impaired intestinal barrier, augmented lesional T lymphocytes and atherosclerosis. This is associated with an increase in serotonin production and a decrease in indole metabolites, thus hijacking Trp for the serotonin pathway. Inhibition of intestinal serotonin production or supplementation with indole derivatives alleviates plaque inflammation and atherosclerosis. In summary, we uncover a pivotal role of intestinal IDO in the fine-tuning of Trp metabolism with systemic effects on atherosclerosis, paving the way for new therapeutic strategies to relieve gut-associated inflammatory diseases. Previous studies suggested the importance of intestinal tryptophan metabolism for gut homeostasis and potential systemic effects but its role in atherosclerosis remains poorly studied. Here, the authors show that the specific deletion of intestinal IDO increases gut inflammation with remote effects on atherosclerosis that can be reversed through inhibiting intestinal serotonin production. [ABSTRACT FROM AUTHOR]

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of 2-(phenyl)indole via the cyclization of 2-(phenylethynyl)aniline in the presence of K2S was established, which was used to prepare 2-(phenyl)indole derivatives in high yields (66%-93%). Mechanistic studies have revealed that a trisulfur radical anion (S3•−) is generated from K2S, which acts as an initiator for the intramolecular addition of the alkyne and the amino group in o-alkynylaniline, ultimately leading to the formation of the indole derivative. This method provides a new way to prepare 2-(phenyl)indoles and a novel application of S3•− in organic synthesis. [ABSTRACT FROM AUTHOR]

This document provides information on the use of photoacid generators (PAGs) in catalysis, specifically in the Friedel-Crafts alkylation of indoles with aldehydes/ketones. The study focuses on diarylethenes and terarylenes as PAGs, which have advantages such as high quantum yields and autonomy. The researchers developed an environmentally friendly method for synthesizing diindolylmethane derivatives with potential antibacterial, antitumor, and antifungal activities. The document also provides detailed information on the synthesis and characterization of various compounds, including their physical properties and spectroscopic data. This information can be useful for researchers studying these compounds and their properties. [Extracted from the article]

Quinolines are biologically and pharmaceutically important N-heterocyclic aromatic compounds, which have broad applications in medicinal chemistry. Thus, their efficient synthesis has attracted extensive attention, and a broad range of synthetic strategies have been established. Of note, gold-catalyzed methodologies for the synthesis of quinolines have greatly advanced this field. Various gold-catalyzed intermolecular annulation reactions, such as annulations of aniline derivatives with carbonyl compounds or alkynes, annulations of anthranils with alkynes, and annulations based on A3-coupling reactions, as well as intramolecular cyclization reactions of azide-tethered alkynes, 1,2-diphenylethynes, and 2-ethynyl N-aryl indoles, have been developed. This review provides an overview of this exciting research area. Typical achievements in reaction methodologies and plausible reaction mechanisms are summarized. [ABSTRACT FROM AUTHOR]

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine‐tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C−C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions. [ABSTRACT FROM AUTHOR]

An efficient one-pot pseudo three component cascade annulation reaction has been devised to generate the fluorescent β-carboline tethered imidazopyrido[3,4-b]indole derivatives. These scaffolds were afforded in high yields via one-pot cascade reaction of diversified β-carboline acetals with NH4Cl through the formation of three C–N bonds in a single operation. The current protocol is step-economical and offers high atom-economy, short reaction time and high structural diversity with excellent yields (57–90%). The synthesized compounds displayed promising photophysical properties and delivered luminescence quantum yield (ΦF) up to 55%. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The privileged C2‐symmetric rigid phenol‐type ligand is more attractive but challenging in asymmetric catalysis. Herein, we designed and synthesized a class of rigid‐featured chiral tridentate Phenol‐2NO ligands, that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone‐based N‐oxide moiety, from readily available L‐prolinamides in operationally simple two steps and up to 44% overall yield. More importantly, using an achiral quinoline derivative as an additive, the newly developed Phenol‐2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II) to form a highly enantioselective catalyst for the asymmetric Michael‐type Friedel‐Crafts alkylation reaction of indoles with 2,3‐dioxopyrrolidines. Excellent yields (up to 90%) and high enantioselectivities (up to 99% ee) are obtained for a wide range of substrates under mild conditions. Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity. This also represented the first activation of phenol‐type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis. [ABSTRACT FROM AUTHOR]

This document provides detailed information about the synthesis and characterization of several compounds, specifically derivatives of spiro[benzofuran-2,3'-indolin]-2'-one. The compounds are described in terms of their physical properties, such as melting point and color, and their chemical structures are provided. The document includes data from nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses, as well as yield and diastereomeric ratio information for each synthesis. These compounds have potential applications in various fields. [Extracted from the article]

Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs. Material and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs. Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2- type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes. Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects. [ABSTRACT FROM AUTHOR]

We report an efficient site-selective synthetic method to C2 and C3 indanyl-substituted indole derivatives via 1,3-dithianyl induced Nazarov-type cyclization. In particular, C2-selective indanyl-substituted indoles were directly obtained by a BF3·Et2O-promoted sequence of intramolecular C3–C2 migration and Nazarov-type cyclization process. [ABSTRACT FROM AUTHOR]

Tempted by the unique medicinal and biological potential of indole‐containing heterocycles, chemists, especially those specializing in heterocycle synthesis and drug discovery, are actively pursuing their efficient construction. This review spotlights the latest advancements in microwave‐assisted (M. W.) synthesis of diverse indole‐based heterocyclic compounds. We systematically categorize the reported methods based on the specific indole substitution patterns. This review concise the microwave assisted synthesis of indole based‐pyridine derivatives, indole based‐pyrimidine, indole based‐oxindole, spiro‐oxindole, Fischer indole Heck‐isomerization derivatives, functionalized indole, substituted indoles, indolyl quinoline, indole triazole and indolylnicotinonitriles derivatives. Ultimately, this review aims to provide organic and medicinal chemists with a concise yet informative guide to recent methodologies employing indole derivatives in the microwave‐powered synthesis of heterocycles. [ABSTRACT FROM AUTHOR]

Here we report B(C6F5)3/CPA‐catalyzed enantioselective aza‐Diels–Alder reaction of 3,3‐difluoro‐2‐Aryl‐3H‐indoles with unactivated dienes to access chiral 10,10‐difluoro‐tetrahydropyrido[1,2‐a]indoles. This protocol allows the formation of pyrazole‐based C2‐quaternary indolin‐3‐ones with high enantioselectivities and regioselectivities. Moreover, gram‐scale synthesis of the 10,10‐difluoro‐tetrahydropyrido[1,2‐a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

AbstractIn recent years, the role of microbial tryptophan (Trp) catabolism in host-microbiota crosstalk has become a major area of scientific interest. Microbiota-derived Trp catabolites positively contribute to intestinal and systemic homeostasis by acting as ligands of aryl hydrocarbon receptor and pregnane X receptor, and as signaling molecules in microbial communities. Accumulating evidence suggests that microbial Trp catabolism could be therapeutic targets in treating human diseases. A number of bacteria and metabolic pathways have been identified to be responsible for the conversion of Trp in the intestine. Interestingly, many Trp-degrading bacteria can benefit from the supplementation of specific dietary fibers and polyphenols, which in turn increase the microbial production of beneficial Trp catabolites. Thus, this review aims to highlight the emerging role of diets and food components, i.e., food matrix, fiber, and polyphenol, in modulating the microbial catabolism of Trp and discuss the opportunities for potential therapeutic interventions via specifically designed diets targeting the Trp-microbiome axis. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive report on the rhodium(III)-catalyzed C–H activation in indole from 2017 to 2022. The direct functionalization of C–H bonds offers a more sustainable and economically sensible route in organic synthesis, reducing the production of hazardous waste. Rhodium has been widely used as a catalyst for C–H functionalization due to its excellent functional group compatibility, versatility, reactivity, and selectivity. The article focuses on the utilization of Rh(III) catalyst for C–H activation of the indole moiety, which is a structurally important building block in natural products and pharmaceutical treatments. Various methods for directed C–H functionalization of indoles, such as C2 activation, alkylation, hydroarylation, and dual C–H activation reactions, are discussed. The text also discusses various methods for the synthesis of carbazole derivatives, benzo[e]indoles, and selective functionalization of indoles through C–H activation. While progress has been made in this area, there are still challenges to overcome, such as the need for harsh reaction conditions and stoichiometric metal oxidants. Continued research in this field is expected to improve reaction conditions and increase overall efficiency. [Extracted from the article]

This document provides a summary of various methods for the synthesis of tetrasubstituted axially chiral alkenes. The methods discussed include urea group-directed organocatalytic dihalogenation, Rh(III)-catalyzed C-H activation and directing group migration, cationic rhodium(I)/H8-BINAP-catalyzed chelation-controlled cycloaddition, Cu/Pd dual catalysis for arylboration, nickel-catalyzed cross-electrophile trans-aryl-benzylation, palladium-catalyzed C-H functionalization, Pd(II)-catalyzed thioether-directed alkenyl C-H olefination, Suzuki-Miyaura cross-coupling, asymmetric N-alkylation, chiral phosphoric acid catalyzed kinetic resolution, and asymmetric allylic substitution-isomerization. The methods demonstrate broad substrate scope and high enantioselectivities, but further research is needed to explore stereodivergent synthesis and applications in pharmaceutical chemistry. [Extracted from the article]

Heyns/Amadori rearrangement allows the synthesis of α-aminocarbonyl compounds from α-hydroxycarbonyls and amines via the generation of an aminoenol intermediate. In the present work, the in situ generated aminoenol intermediate has been efficiently trapped with ketones/aldehydes for the construction of N-heterocycles. This method offers access to various substituted indole derivatives with a high level of regioselectivity through the intramolecular trapping of the aminoenol intermediate derived from o-acyl/formylanilines and α-hydroxydimethylacetals/ketals followed by rearrangement/aromatization in the presence of acid. Important features include the use of α-hydroxydimethylacetal/ketal as an α-hydroxycarbonyl equivalent, excellent regiocontrol, good functional group tolerance, selective synthesis of acylindoles, gram-scale synthesis, and synthesis of higher analogues of indoles and anti-tumor agent. [ABSTRACT FROM AUTHOR]

A series of cyclometallated gold(III) complexes 21–27 of general formula [Au(dppta)(azdtc)Cl] (dppta = N,N-diisopropyl-P,P-diphenylphosphinothioic amide-κ2C,S; azdtc = azol(in)ium-2-dithiocarboxylate-κ1S) were prepared and characterized by spectroscopic and diffractometric techniques. Treatment of [Au(dppta)(azdtc)Cl] complexes with methanol led to their quantitative transformation into a novel family of (C^S, S^S)-cyclometallated gold(III) complexes of general formula [Au(dppta)(azmtd)] (azmdt = azol(in)ium-2-(methoxy)methanedithiol-κ2S,S) 28–34. All the [Au(dppta)(azdtc)Cl] complexes 21–27 catalyzed the alkylation of indoles, whereas [Au(dppta)(azmtd)] complexes 28–34 were inactive. Among the synthesized derivatives, complex 22 displayed the highest catalytic activity, leading to a series of functionalized indoles in excellent yields. [ABSTRACT FROM AUTHOR]

Fungi possess well-developed secondary metabolism pathways that are worthy of in-depth exploration. The One Strain Many Compounds (OSMAC) strategy is a useful method for exploring chemically diverse secondary metabolites. In this study, continued chemical investigations of the marine red algae-derived endophytic fungus Penicillium oxalicum 2021CDF-3 cultured in PDB media yielded six structurally diverse indole derivatives, including two new prenylated indole alkaloids asperinamide B (1) and peniochroloid B (5), as well as four related derivatives (compounds 2-4 and 6). The chemical structures of these compounds, including the absolute configurations of 1 and 5, were determined by extensive analyses of HRESIMS, 1D and 2D NMR spectroscopic data, and TDDFT-ECD calculations. Compound 1 was found to possess an unusual 3-pyrrolidone dimethylbenzopyran fused to the bicyclo[2.2.2]diazaoctane moiety, which was rare in previously reported prenylated indole alkaloids. In vitro cytotoxic experiments against four human tumor cell lines (HeLa, HepG2, FADU, and A549) indicated that 1 strongly inhibited the FADU cell line, with an IC50 value of 0.43 ± 0.03 µM. This study suggested that the new prenylated indole alkaloid 1 is a potential lead compound for anti-FADU drugs. [ABSTRACT FROM AUTHOR]

Lentiviral vectors derived from human immunodeficiency virus type I are widely used to deliver functional gene copies to mammalian cells for research and gene therapies. Post-transcriptional splicing of lentiviral vector transgene in transduced host and transfected producer cells presents barriers to widespread application of lentiviral vector-based therapies. The present study examined effects of indole derivative compound IDC16 on splicing of lentiviral vector transcripts in producer cells and corresponding yield of infectious lentiviral vectors. Indole IDC16 was shown previously to modify alternative splicing in human immunodeficiency virus type I. Human embryonic kidney 293T cells were transiently transfected by 3rd generation backbone and packaging plasmids using polyethyleneimine. Reverse transcription-quantitative polymerase chain reaction of the fraction of unspliced genomes in human embryonic kidney 293T cells increased up to 31% upon the indole's treatment at 2.5 uM. Corresponding yield of infectious lentiviral vectors decreased up to 4.5-fold in a cell transduction assay. Adjusting timing and duration of IDC16 treatment indicated that the indole's disruption of early stages of transfection and cell cycle had a greater effect on exponential time course of lentiviral vector production than its reduction of post-transcriptional splicing. Decrease in transfected human embryonic kidney 293T proliferation by IDC16 became significant at 10 uM. These findings indicated contributions by early-stage transfection, cell proliferation, and post-transcriptional splicing in transient transfection of human embryonic kidney 293T cells for lentiviral vector production. [ABSTRACT FROM AUTHOR]

Utilizing iron chloride as a Lewis acid catalyst, we developed a straightforward and mild oxidative cross-coupling reaction between quinoxalinones and indoles, yielding a series of versatile 3-(indol-3-yl)quinoxalin-2-one derivatives. This approach allows for the incorporation of a wide array of functional groups into the final products, demonstrating its synthetic versatility. Notably, the method was successfully scaled up to gram-scale reactions while maintaining high yields. Our mechanistic investigation indicates that iron chloride serves as a catalyst to facilitate the formation of key intermediates which subsequently undergo oxidation to afford the desired products. The merits of this protocol include its cost effectiveness, operational simplicity, and the ease of product isolation via filtration. [ABSTRACT FROM AUTHOR]

The total synthesis of alternatamines B and D is outlined. Alternatamine B demonstrates moderate antibacterial activity across a broad spectrum of bacteria. Both alternatamines B and D feature an intriguing 5,6‐dibromoindole skeleton, derived from a four‐step sequence starting with 3,4‐dibromoaniline and achieving a total yield of 48 %. The key steps involve: (a) functional group modifications, including iodination, of 3,4‐dibromoaniline with two bromine substituents to obtain the Sonogashira precursor; (b) indole synthesis through Sonogashira coupling and 5‐endo‐dig cyclization; (c) carbon chain extension and introduction of the nitrogen atom at the C3 of the indole. Subsequently, the tryptamine analogue was coupled with an L‐leucine derivative through amide bond formation after deprotection, yielding alternatamide D. The first total synthesis of alternatamine B was also achieved by selectively introducing a bromine substituent at the C2 of the indole, employing optimal bromination conditions. [ABSTRACT FROM AUTHOR]

A prominent heterocyclic system found in medications and natural goods is indoles. Due to the significance of this important ring system, a fresh batch of unique indole derivatives was created using indole carbohydrazide. The triazole moiety of indole derivative (3) is produced by reacting carbohydrazide with carbon disulfide in alkaline conditions, followed by hydrazine treatment. In addition to synthesizing additional derivatives, indole-bearing triazole (3) was condensed with aromatic aldehydes to create the indole derivatives (4a–c). Mass spectra, 1HNMR, 13CNMR, and infrared spectroscopy were used to diagnose all produced derivatives. An MTT assay was employed to test the derivatives against MCF-7 cells. The findings demonstrated the inhibitory action of compounds 5a and 5b, with IC50 values of 42.6 ± 0.33 µM and 27.3 ± 0.28, respectively. Affinity energy and the interaction between the investigated chemicals and receptor (CDK4 ID: 2w96) were ascertained by studying molecular docking. The chemical structure-physicochemical-pharmacokinetic relationship provides useful insight for medicinal chemists to design indole-triazole derivatives with acceptable drug-like and pharmacokinetic properties.

Abstract Background The host–microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, and microbial tryptophan metabolites are potent modulators of host physiology. However, whether and how these metabolites mediate host–microbiota interactions, particularly in terms of inter-microbial communication, remains unclear. Results Here, we have demonstrated that indole-3-lactic acid (ILA) is a key molecule produced by Lactobacillus in protecting against intestinal inflammation and correcting microbial dysbiosis. Specifically, Lactobacillus metabolizes tryptophan into ILA, thereby augmenting the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Notably, ILA, IPA, and IAA possess the ability to mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10−/− spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria (e.g., Clostridium), as well as the mRNA expression of acyl-CoA dehydrogenase and indolelactate dehydrogenase in vivo and in vitro, resulting in an augmented production of IPA and IAA. Furthermore, a mutant strain of Lactobacillus fails to protect against inflammation and producing other derivatives. ILA-mediated microbial cross-feeding was microbiota-dependent and specifically enhanced indole derivatives production under conditions of dysbiosis induced by Citrobacter rodentium or DSS, but not of microbiota disruption with antibiotics. Conclusion Taken together, we highlight mechanisms by which microbiome-host crosstalk cooperatively control intestinal homoeostasis through microbiota-derived indoles mediating the inter-microbial communication. These findings may contribute to the development of microbiota-derived metabolites or targeted “postbiotic” as potential interventions for the treatment or prevention of dysbiosis-driven diseases. Video Abstract

An efficient method has been developed to facilitate the addition‐ring opening cascade reaction of vinylogous oxindole, resulting in the synthesis of a variety of aza‐bicyclic maleimide derivatives with high yields and exceptional diastereoselectivities. Furthermore, the product could be effectively and easily transformed into the difluoromethylenecyclohexane skeleton through a dehydrofluorination process. This methodology demonstrates significant potential for the synthesis of aza‐bicyclic maleimide skeleton, which possesses biological or pharmaceutical activity. [ABSTRACT FROM AUTHOR]

We present an Ugi multicomponent approach to explore the chemical space around Aspidosperma‐type monoterpene indole alkaloids. By variation of the isocyanide and carboxylic acid inputs we demonstrate the rapid generation of molecular diversity and the possibility to introduce handles for further modification. The key Ugi three‐component reaction showed full diastereoselectivity towards the cis‐fused ring system, which can be rationalized by DFT calculations that moreover indicate that the reaction proceeds via a Passerini‐type hydrogen bonding mechanism. Several post‐Ugi modifications were also performed, including Pictet‐Spengler cyclization to highly complex nonacyclic natural product hybrid scaffolds. [ABSTRACT FROM AUTHOR]

A protocol for trans-hydroboration of indole derivatives using heterogeneous photocatalysis with NHC-borane has been developed, addressing a persistent challenge in organic synthesis. The protocol, leveraging high crystalline vacancy-engineered polymeric carbon nitride as a catalyst, enables diastereoselective synthesis, expanding substrate scope and complementing existing methods. The approach emphasizes eco-friendliness, cost-effectiveness, and scalability, making it suitable for industrial applications, particularly in renewable energy contexts. The catalyst's superior performance, attributed to its rich carbon-vacancies and well-ordered structure, surpasses more expensive homogeneous alternatives, enhancing viability for large-scale use. This innovation holds promise for synthesizing bioactive compounds and materials relevant to medicinal chemistry and beyond. Dearomative hydroboration of predominantly existing indole derivatives provides a straightforward strategy to synthesize boryl indolines, but developing eco-friendly methods for remains challenging. Here, the authors develop a method for heterogeneous photocatalytic trans-hydroboration of indole derivatives with NHC-borane. [ABSTRACT FROM AUTHOR]

When a mixture containing 1‐halo‐1‐alkyne, a dinucleophilic agent, and a base (Cs2CO3 or K3PO4) was heated in DMF, regio‐ and stereo‐selective nucleophilic addition of the dinucleophilic agent to the acetylenes occurred. This reaction yielded (Z,Z)‐bis(haloalkene), which subsequently underwent Pd‐catalyzed cyclization through C−H bond activation, resulting in the formation of two‐oxygen‐ or ‐nitrogen‐containing hetero‐π‐conjugated compounds. N‐(5‐Hydroxynaphthalen‐1‐yl)methanesulfonamide was treated with 2‐phenyl‐1‐chloroethyne followed by 1‐chloro‐1‐hexadecyne. After these reactions, Pd‐catalyzed double C−H cyclization was employed to produce 1H‐2‐phenyl‐7‐tetradecylbenzofuro[7,6‐g]indole. Notably, this compound transformed into a fan‐shaped structure at 86 °C and transitioned into a smectic A phase characterized by a layered structure. [ABSTRACT FROM AUTHOR]