Indole Molecules Research Articles

Green Synthesis of Iron-Based Nanoparticles Using Pomegranate Leaf Extracts: Characterization, Biomolecules and Indole Removal

This study investigates the synthesis of iron-based nanoparticles (Fe NPs) using pomegranate leaf extracts and their application in removing indole, a persistent organic pollutant commonly found in wastewater. The physicochemical properties of the synthesized Fe NPs and the active biomolecules in the pomegranate leaf extracts were comprehensively characterized. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) analyses revealed that the Fe NPs exhibited quasi-spherical shapes, with sizes ranging from 75 to 105 nm. Energy-Dispersive X-ray Spectroscopy (EDS) confirmed a homogeneous distribution of elements, including C, O, Fe, and S, on the nanoparticle surfaces, with weight percentages of 43.59%, 42.95%, 12.58%, and 0.88%, respectively. Fourier-transform infrared spectroscopy (FTIR) identified key functional groups like −OH, −COOH, and −C=O, which are essential for the capping and stabilization of the nanoparticles. Biomolecules such as ellagic acid (C14H6O8) and gallic acid (C7H6O5) functioned as reducing agents, improving nanoparticle dispersion and preventing aggregation. The synthesized Fe NPs quickly achieved 45.5% removal of indole within just 20 min and maintained a stable removal efficiency of approximately 51.4% after 90 min. This performance was attributed to the synergetic interaction between the biomolecules and the nanoparticles, with the monolayer adsorption of indole molecules on the Fe NP surfaces likely setting an upper limit on the maximum achievable removal efficiency. It appears from this study that pomegranate leaf extracts can be effectively utilized to synthesize Fe NPs as a novel and eco-friendly approach, demonstrating promising potential for the rapid removal of indole from aqueous solutions.

An Experimental Dynamic Investigation of the Influence of Melatonin, Serotonin and Tryptophan on the Stability of the DNA Structure

Background: Small molecules play a crucial role in the exploration of physiological pathways and in drug development by targeting deoxyribonucleic acid (DNA). DNA is a central focus for both endogenous and exogenous ligands, which interact directly or indirectly to regulate transcription and replication processes, thus controlling genetic expression in specific cells. Among these molecules, indole derivatives like tryptophan, serotonin, and melatonin are notable for their widespread presence in nature and significant biological effects. Tryptophan, an essential amino acid, serves as a vital structural element in proteins and a precursor for bioactive compounds like serotonin and melatonin, which impact various physiological functions. Methods: Experimental studies have been conducted to reveal the interaction mechanisms of these endogenous indole derivatives with calf thymus DNA (ct-DNA). These investigations involve viscosity measurements and analysis of double-stranded DNA behavior in the presence of indole molecules, using spectrophotometric UV absorption techniques to assess their impact on DNA stability. Additionally, the influence of calcium and magnesium ions on the resulting complexes of these indole derivatives with ct-DNA has been evaluated. Molecular docking validated our findings, offering additional insights into potential DNA–ligand interactions. Utilizing a crystallographic oligomer with an intercalation gap improved docking accuracy, distinguishing intercalation from groove recognition and enhancing assessment precision. Results: Our study offers detailed insights into the interaction patterns of the indole derivatives with DNA and is highly supported by molecular docking analyses: the indole derivatives were predominantly localized between C and G, interacting via π-π interactions and hydrogen bonds and aligning with known data on conventional intercalators. These findings underscore the importance of small compounds’ planar structure and appropriate size, facilitating tight insertion between adjacent base pairs and disrupting regular DNA stacking. Conclusions: Indoles’ physiological roles and potential as drug candidates targeting specific pathways are highlighted, emphasizing their significance as ubiquitous molecules with the ability to modulate biological effects on DNA structure.

Indole derivatives efficacy and kinetics for inhibiting carbon steel corrosion in sulfuric acid media

The global prevalence of metal corrosion is a significant challenge due to its detrimental effect. Environmentally friendly and non-hazardous alternatives for harmful and poisonous synthetic corrosion inhibitors are urgently necessary due to increasing environmental concerns and regulations prohibiting their application. In this study, indole molecules were employed as carbon steel corrosion inhibitors in acidic conditions. Gravimetrical and scanning electronic microscope (SEM) analysis was used in a preliminary investigation of indole as an organic inhibitor. The results revealed that adding indole to carbon steel before exposing it to sulfuric acid slowed and induced resistance to corrosion. The indole affixed themselves to the steel carbon surfaces, producing a barrier/protection for carbon steel. The efficacy of the indole in preventing corrosion was determined through the weight loss method. Temperature and inhibitory concentration effects on inhibition effectiveness under varying parameters were also reported. The temperatures employed were between 298 K and 328 K, while the inhibitor concentrations ranged from 1.2 × 10−3 M to 7.6 × 10−3 M, and both parameters significantly influenced corrosion inhibition effectiveness. The inhibitory mixture attained optimum efficacy in inhibiting corrosion, at 81 %, when the lowest and highest respective temperature and concentration were applied. The kinetic analysis was conducted under a range of temperatures to determine the reaction mechanisms of the inhibitor. The thermal adsorption isotherm of the inhibitor indicated that the surface adhered to Langmuir's adsorption isotherm. Additionally, investigations on corrosion and inhibition using the electrochemical impedance spectroscopy method (EIS) were conducted. This study can provide in-depth knowledge for advancing inhibitory science and engineering to enhance corrosion resistance in acidic media.

Investigating the molecular interactions of 11-substituted-1-(4-chlorophenyl)-8H-indolo[3,2-c][1,2,4]triazolo[3,4-a]isoquinolines for Antimicrobial Potential: Synthesis, Spectral, In vitro and In silico study interpretations

Indole molecules are one of the important scaffolds in the discovery and development of new drugs. We herein described a synthesis of new 11-substituted-1-(4-chlorophenyl)-8H-indolo[3,2-c][1,2,4]triazolo[3,4-a]isoquinoline 6 (a-h). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and mass. The DFT calculations were taken for the selected molecules using CAM-B3LYP hybrid functional with a 6–31+g(d) all-electron basis set using the Gaussian 09 package. The drug-likeness calculations were explained for the synthesized derivatives. The compounds 6b, 6c and 6 g exhibited excellent antibacterial, antifungal and anti-TB activities against tested pathogens at MIC 3.125 μg/ml. Furthermore, molecular docking studies of these compounds against S. aureus Gyrase (PDB ID:2XCT), Staphylococcus aureus tyrosyl-tRNA synthetase (PDB ID:1JIJ), and Mycobacterium tuberculosis enoyl reductase (INHA) (PDB ID:4TZK), revealed the potential binding mode of the ligands to the site of the appropriate targets. Finally, drug likeness and SAR studies were disclosed. Lastly, the protein stability, fluctuations of APO-Protein, and protein-ligand complexes were investigated through molecular dynamics simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.

Assessing indole derivative molecules as dual acetylcholinesterase and butyrylcholinesterase inhibitors through In Vitro inhibition and molecular modelling studies

Alzheimer's Disease (AD) is the most common type of dementia that develops with age, threatens the quality of life, is increases in number around the world, and has no effective treatment. The most important therapeutic targets in drug development studies for the treatment of AD are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The inadequacy of existing AChE and BChE inhibitors in the treatment of AD has led to the need to identify new AChE/BChE inhibitors with fewer side effects. In this study, considering the pharmacological importance indole derivatives, inhibition effects of some indole derivative molecules (a-e) on AChE and BChE activity were investigated. IC50 values of a-e against AChE were found to be 0.480 µM, 1.682 µM, 0.916 µM, 1.093 µM, 0.340 µM, respectively. On the other hand, IC50 values of compounds a-e on BChE activity were determined as 2.18 µM, 4.49 µM, 2.28 µM, 6.36 µM, 1.940 µM, respectively. As a result, it was seen that indole derivatives (a-e) showed strong inhibition effect on both enzymes. Additionally, these inhibition results were supported by molecular modelling studies. As a conclusion, results of this study will contribute to studies on the synthesis of new indole-derived AChE and BChE inhibitors for the treatment of AD.

Synthesis of 2-Substituted Indoles via Migration Reaction of 3-Substituted Indoles with Triflic Acid.

This study showcases the 1,2-migration reactions of alkyl and aryl groups on the indole molecule. Trifluoromethanesulfonic acid effectively facilitates the migration of the substituent from C3- to C2-position of the indole structure. The resulting C2-substituted indoles offer a valuable pathway for the synthesis of natural products and medicinal compounds.

New Perspectives on the Role and Therapeutic Potential of Melatonin in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. It is essential to develop novel interventions to prevent/delay CVDs by targeting their fundamental cellular and molecular processes. Melatonin is a small indole molecule acting both as a hormone of the pineal gland and as a local regulator molecule in various tissues. It has multiple features that may contribute to its cardiovascular protection. Moreover, melatonin enters all cells and subcellular compartments and crosses morphophysiological barriers. Additionally, this indoleamine also serves as a safe exogenous therapeutic agent. Increasing evidence has demonstrated the beneficial effects of melatonin in preventing and improving cardiovascular risk factors. Exogenous administration of melatonin, as a result of its antioxidant and anti-inflammatory properties, has been reported to decrease blood pressure, protect against atherosclerosis, attenuate molecular and cellular damage resulting from cardiac ischemia/reperfusion, and improve the prognosis of myocardial infarction and heart failure. This review aims to summarize the beneficial effects of melatonin against these conditions, the possible protective mechanisms of melatonin, and its potential clinical applicability in CVDs.

Acid-Promoted Domino Access to Substituted Benzo[b]carbazoles.

Herein, a straightforward Bro̷nsted acids-promoted domino pathway to build substituted benzo[b]carbazoles has been described from easily accessible ortho-formyl (or ortho-acyl) cinnamate esters and indoles. Noticeably, the protocol was amenable to protecting group-free indoles. Notably, this methodology is based on a single-pot regioselective construction of two new C-C bonds and aromatization sequences under mild and metal-free reaction conditions. The mechanistic studies suggested the initial formation of bis-indole substituted intermediate via a dual aromatic substitution with two indole molecules at the carbonyl carbon of ortho-formyl (or ortho-acyl) cinnamate ester followed by intramolecular cyclization and aromatization with exclusion of a second indole molecule. Besides, the efficacy of this approach was also illustrated by scale-up and derivatization reactions, including the photophysical properties study.

A general approach to construct selenopheno[3,2-b]indole-cored molecules using Fischer indolization.

A wide series of various selenopheno[3,2-b]indole-based compounds, including 2-aryl-substituted selenopheno[3,2-b]indoles as well as derivatives of benzo[4,5]selenopheno[3,2-b]indole, pyrido[3',2':4,5]selenopheno[3,2-b]indole, pyrazino[2',3':4,5]selenopheno[3,2-b]indole and chromeno[3',4':4,5]selenopheno[3,2-b]indol-6-one, were prepared from the appropriate 3-aminoselenophen-2-carboxylates via a one-pot two-step procedure based on the Fischer indole synthesis. The present synthetic strategy includes the conversion of 3-aminoselenophen-2-carboxylates into 2-unsubstituted 3-aminoselenophenes, their C-2 protonation to form selenophen-3(2H)-iminium cations, and the reaction of these iminium intermediates with arylhydrazines to obtain arylhydrazones of selenophen-3(2H)-ones followed by their Fischer indolization affording selenopheno[3,2-b]indole molecules.

Melatonin serves as a novel treatment in bladder fibrosis through TGF-β1/Smad and EMT.

Melatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms. MEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-β1 (TGF-β1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-β1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed. In vitro, we found that TGF-β1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-β1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis. Melatonin attenuates bladder fibrosis by blocking the TGF-β1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

Synthesis, Characterization, and Biological Evolution Indole Molecules

Synthesis, Characterization, and Biological Evolution Indole Molecules

Photophysical Processes in Indole Molecules in Ethanol at 77 K During Excitation at the Long-Wave Edge of the Absorption Spectrum

Photophysical Processes in Indole Molecules in Ethanol at 77 K During Excitation at the Long-Wave Edge of the Absorption Spectrum

SOME CHARICTERISTIC OF MICROBIAL INDOLE EXTRACTED FROM PATHOGENIC E. COLI IN COMPARABLE WITH STANDARD ONE

Indole molecules as a signal has an important role in bacterial ecosystem, this study was aimed and conducted on the extraction and partial purification of indole from pathogenic E. coli and study several indole characterizations parameters compared with synthetic standard one. A total of 134 urine specimens and other stool 152 specimens were obtained from Al-Ramadi Hospitals, during the period from November / 2018 to March / 2019.The results show the percentage of isolated E. coli from Urinary tract infection was 100 (74.6%)/134, While 152 (100%)/ 152 are isolated from stool. Primary and secondary screening concluded, there are ten isolates are considered as the best in production of indole. The most producible one is selected with indole concentration 165.667 µM/ml. Also, indole production needs several optimal parameters to elevate its production, the study improved that the best pH is 9, temperature is 35 °C, incubation period is 18 hrs. and indole concentration is directly proportional with the amount of tryptophan added. Thin layer chromatography result reveals that no significant difference between extracted indole Rf 0.9 and 0.91 of synthetic standard one. Fourier-Transform-Infrared Spectroscopy, the results show there are some differences in the analysis in some structural positions.

Crystal structure and Hirshfeld surface analysis of 3-(bromo-meth-yl)-2-[1,2-di-bromo-2-(6-nitro-benzo[d][1,3]dioxol-5-yl)eth-yl]-1-(phenyl-sulfon-yl)-1H-indole chloro-form 0.585-solvate.

The title indole derivative, C24H17Br3N2O6S, crystallizes with a partial occupancy [0.585 (4)] CHCl3 solvent mol-ecule. The dihedral angles between the indole ring system and pendant nitro-benzodioxolane rings system and phenyl-sulfonyl ring are 4.81 (14) and 72.24 (19)°, respectively. In the crystal, the indole mol-ecules are linked to each other and to the chloro-form mol-ecule by weak C-H⋯O, C-H⋯Cl, C-H⋯π, C-Br⋯π and C-Cl⋯π and aromatic π-π stacking inter-actions. A Hirshfeld surface analysis was carried out and the inter-molecular contacts with the most significant contributions are H⋯O/O⋯H (24.3%), H⋯H (18.4%), Br⋯H/H⋯Br (16.8%) and C⋯H/H⋯C (8.4%).

Probing ground and low-lying excited states for indole derived compounds of potential herbicide action

In this work, we present a study on a series of recently synthesized indole derived compounds that were previously suggested by experimental tests as having herbicidal action. Density functional theory (DFT) and its time-dependent formalism (TD-DFT) were used for investigating ground and excited state properties, respectively. The M06-2X and CAM-B3LYP exchange-correlation functionals were used with the aug-cc-pVTZ basis set. Computations were performed in the gas-phase, water, and dimethyl sulfoxide. Solvation was found to play minor effects on the ground state structure of any given compound. On the other hand, solvation was found to cause a decrease in the excitation energies of the lowest-lying excited singlet states of almost all the compounds. More importantly, all the indole derived compounds presented excitation energies that are considerably lower than those determined for their parent molecule. For instance, the lowest-lying excited singlet was probed at 3.45 eV in the case of 6-chloro-8-nitro-2,3,4,9-tetrahydro-1H-carbazole (compound 15a) versus 5.00 eV for the corresponding state of the indole molecule, both values determined at the TD-DFT/M06-2X/aug-cc-pVTZ level in water. In addition, compound 15a along with 5-chloro-2,3-dimethyl-7-nitro-1H-indole (15b) presented three excited states (each) that are likely to be accessed (having oscillator strength ≳0.1 at the TD-DFT/M06-2X/aug-cc-pVTZ level of theory in water) among the five respective lowest-lying excited singlets. The existence of various excited states accessible at lower energies may provide competing alternative paths to the chlorophyll-solar radiation interaction, in detrimental manner to the photosynthetic process; an observation in agreement to the previous experimental findings. Frontier orbital analysis suggested electron delocalization (advent from structural modifications) to be responsible for lowering the excitation energies.

Murine macrophage-based iNos reporter reveals polarization and reprogramming in the context of breast cancer.

As part of the first line of defense against pathogens, macrophages possess the ability to differentiate into divergent phenotypes with varying functions. The process by which these cells change their characteristics, commonly referred to as macrophage polarization, allows them to change into broadly pro-inflammatory (M1) or anti-inflammatory (M2) subtypes, and depends on the polarizing stimuli. Deregulation of macrophage phenotypes can result in different pathologies or affect the nature of some diseases, such as cancer and atherosclerosis. Therefore, a better understanding of macrophage phenotype conversion in relevant models is needed to elucidate its potential roles in disease. However, there are few existing probes to track macrophage changes in multicellular environments. In this study, we generated an eGFP reporter cell line based on inducible nitric oxide synthase (iNos) promoter activity in RAW264.7 cells (RAW:iNos-eGFP). iNos is associated with macrophage activation to pro-inflammatory states and decreases in immune-suppressing ones. We validated the fidelity of the reporter for iNos following cytokine-mediated polarization and confirmed that reporter and parental cells behaved similarly. RAW:iNos-eGFP cells were then used to track macrophage responses in different in vitro breast cancer models, and their re-education from anti- to pro-inflammatory phenotypes via a previously reported pyrimido(5,4-b)indole small molecule, PBI1. Using two mouse mammary carcinoma cell lines, 4T1 and EMT6, effects on macrophages were assessed via conditioned media, two-dimensional/monolayer co-culture, and three-dimensional spheroid models. While conditioned media derived from 4T1 or EMT6 cells and monolayer co-cultures of each cancer cell line with RAW:iNos-eGFP cells all resulted in decreased fluorescence, the trends and extents of effects differed. We also observed decreases in iNos-eGFP signal in the macrophages in co-culture assays with 4T1- or EMT6-based spheroids. We then showed that iNos production is enhanced in these cancer models using PBI1, tracking increased fluorescence. Collectively, this work demonstrates that this reporter-based approach provides a facile means to study macrophage responses in complex, multicomponent environments. Beyond the initial studies presented here, this platform can be used with a variety of in vitro models and extended to in vivo applications with intravital imaging.

Photo-Induced In Situ Generation of Brønsted Acid for Catalytic Friedel-Crafts Alkylation of Indoles.

A photo-induced indole 2-alkylation reaction was developed with unactivated stereo-congested alkenes used as the Friedel-Crafts alkylation reagent. The neutral, traceless and inexpensive perfluoroalkyl iodide C4 F9 I was used as the radical initiator in catalytic amount under irradiation by a blue LED light. Brønsted acids are in situ generated from the radical transfer reactions between the indole substrates and the perfluoroiodide catalyst. A variety of 2-branched alkylated indole molecules could be obtained from this approach in generally good efficiencies, with a broad scope of functional groups well tolerated. Mechanistic studies via both experimental and computational methods indicate that the reaction was accelerated by the protons generated from the crack of the indole-derived radical cation species.

A DFT evaluation of molecular reactivity of volatile organic compounds in support of chemical ionization mass spectrometry

Gas-phase molecular properties of volatile organic compounds (VOCs) play an important role in the selection of gas-phase reagent ions for chemical ionization mass spectrometry (CI-MS). Chemical ionization-based mass spectrometry techniques such as proton transfer reaction mass spectrometry (PTR-MS) and selected ion flow-tube mass spectrometry (SIFT-MS) provide real-time, rapid, and online detection and quantification of VOCs using thermodynamics and kinetics of ion-molecule gas-phase reactions. We apply hybrid density functional theory (DFT) to compute proton affinity (PA), ionization energy (IE), and global reactivity parameters for VOCs, which are widely regarded as the primary sources of taints and off-flavors in wine. Atomic polar tensor (APT) charges and total energies at the stationary point for neutral and protonated molecules are also computed. PA and IE values determine the CI-MS mode of reactions, either proton transfer or electron transfer from the reagent gas ions to VOCs. Global reactivity parameters, such as chemical potential (μ), chemical hardness (η), softness (σ), and electrophilic nature (ω) as obtained from frontier molecular orbitals, are considered useful in rationalizing the chemical reactivity patterns of the molecules. A benchmark calculation of indole molecule with MP2, B3LYP, and M06-2X DFT methods at thermodynamically and kinetically stable protonation sites further supports the applied DFT method. Since limited data are available on computed parameters, the reported values would support CI-MS quantification of trace-level VOCs not only in wine but also in various food products.

Design, synthesis, and anticancer evaluation of 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles.

A series of 1-benzo[1,3]dioxol-5-yl-indoles bearing 3-N-fused heteroaryl moieties have been designed based on literature reports of the activity of indoles against various cancer cell lines, synthesized via a Pd-catalyzed C-N cross-coupling, and evaluated for their anticancer activity against prostate (LNCaP), pancreatic (MIA PaCa-2), and acute lymphoblastic leukemia (CCRF-CEM) cancer cell lines. A detailed structure-activity relationship study culminated in the identification of 3-N-benzo[1,2,5]oxadiazole 17 and 3-N-2-methylquinoline 20, whose IC50 values ranged from 328 to 644nM against CCRF-CEM and MIA PaCa-2. Further mechanistic studies revealed that 20 caused cell cycle arrest at the S phase and induced apoptosis in CCRF-CEM cancer cells. These 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles may serve as a template for further optimization to afford more active analogs and develop a comprehensive understanding of the structure-activity relationships of indole anticancer molecules.

Synthesis of Indole-Fused Dihydrothiopyrano Scaffolds via (3 + 3)-Annulations of Donor-Acceptor Cyclopropanes with Indoline-2-Thiones.

A new methodology for the synthesis of N-haloindole-fused dihydrothiopyrano derivatives via (3 + 3)-annulation of donor-acceptor cyclopropanes (DACs) with indoline-2-thiones in the presence of Sc(OTf)3 as a Lewis acid catalyst has been developed. This protocol provides a variety of indole-fused dihydrothiopyrano molecules in good to excellent yields, which architecturally resemble other indole-fused tricyclic molecules having potential medicinal value. In addition, we have described a detailed reaction mechanism and transformation of the furnished product into N-fused thiazino indole molecule.