Quinoline Compounds Research Articles

Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features

Objectives: Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of Plasmodium falciparum and Plasmodium vivax Methods: A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating P. falciparum and P. vivax. The mechanism of action and SAR of these compounds were analyzed Results: Quinoline-based antimalarials demonstrated significant effectiveness in eliminating P. falciparum parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite’s acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results. Conclusion: Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against P. falciparum and P. vivax parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.

Investigation of the cytotoxic and antimicrobial properties of new quinoline peptide conjugates

Background: Cancer is one of the most important health problems causing deaths in Turkey and the world. Nowadays, many treatment methods such as radiotherapy and chemotherapy are applied in cancer patients. Quinoline and its derivatives, which belong to heterocyclic compounds, have many biological activities for drug development. Quinoline compounds play a crucial role in the development of antitumor drugs due to their anticancer activity. Materials and Methods: In this study, the cytotoxic effects of synthesized seven different quinoline derivatives on lung cancer (A549) and healthy lung epithelial cell (BEAS2B), liver cancer (Hep 3B), and endothelial cell (HUVEC) were determined. Different concentrations were applied and IC50 values were calculated at different time courses. The antimicrobial activites of the compounds were also determined. Results: The IC50 values of compound 2 on the A549 cell line were determined to be 10.48 μg/mL, 9.738 μg/mL, and 10.14 μg/mL. IC50 values of compound 6 on the same cell line were determined to be 7.307 µg/mL, 9.888 µg/mL, 10.63 µg/mL. Conclusions: Compounds 2 and 6 had a cytotoxic effect on the BEAS2B cell line. The antimicrobial activity of the compounds was determined by the minimum inhibition concentration method on different strains of bacteria and yeast. The compounds showed no antimicrobial activity on bacteria and yeast.

Quinoline Derivatives as Promising Scaffolds for Antitubercular Activity: A Comprehensive Review.

Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is also known as benzpyridine, benzopyridine, and 1-azanaphthalene. It has a benzene ring fused with a pyridine ring, and both rings share two carbon atoms. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. This article is expected to have a significant impact on the advancement of effective antitubercular drugs. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility comes from their ability to bind with the receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, anti-tumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain nitrogen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of significant properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study emphasizes the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.

Quinoline Derivatives in Discovery and Development of Pesticides.

Finding highly active molecular scaffold structures is always the key research content of new pesticide discovery. In the research and development of new pesticides, the discovery of new agricultural molecular scaffold structures and new targets still faces great challenges. In recent years, quinoline derivatives have developed rapidly in the discovery of new agriculturally active molecules, especially in the discovery of fungicides. The unique quinoline scaffold has many advantages in the discovery of new pesticides and can provide innovative and feasible solutions for the discovery of new pesticides. Therefore, we reviewed the use of quinoline derivatives and their analogues as molecular scaffolds in the discovery of new pesticides since 2000. We systematically summarized the agricultural biological activity of quinoline compounds and discussed the structure-activity relationship (SAR), physiological and biochemical properties, and mechanism of action of the active compounds, hoping to provide ideas and inspiration for the discovery of new pesticides.

Phosphine-Catalyzed Domino Annulation of γ-Vinyl Allenoates: Synthesis of Tetrahydrofuro[3,2-c]quinoline Derivatives.

A novel phosphine-catalyzed domino annulation reaction of γ-vinyl allenoates and o-aminotrifluoacetophenones for the construction of terahydrofuro[3,2-c]quinoline derivatives has been developed. In this domino reaction, two kinds of terahydrofuro[3,2-c]quinoline compounds containing CF3 groups were obtained with good yields under mild conditions, three new C-N, C-C, and C-O bonds can be built in one step, and the reaction selectivity is achieved by adjusting the reaction conditions. Furthermore, preliminary studies on an asymmetric variant of this reaction proceeded with moderate enantioselectivity.

Ligand‐promoted dehydrogenative coupling of γ‐/β‐amino alcohols with ketones to N‐heterocycles via molybdenum catalysts

Molybdenum‐based efficient and broadly applicable catalytic system is presented for the dehydrogenative coupling of γ‐/β‐amino alcohols with ketones. In particular, complex Mo(CO)6 in combination with Xantphos and t‐BuOK as base provides direct synthesis of structurally diverse quinoline, pyridine, and pyrrole compounds (total 55 examples) with isolated yields up to 92%. Low catalyst loading, cost‐effective, and high catalytic activities with high tolerance to stand with diverse functional groups are additional features of these molybdenum catalysts exhibiting high efficacy to replace the precious metal catalysts such as ruthenium and iridium. Furthermore, the DFT and experimental studies were explored for the reaction mechanism which can assist in broadening the scope of the molybdenum catalysts for different transformation reactions.

F25, a novel synthetic quinoline derivative, inhibits tongue cancer cell invasion and survival by the PPAR pathway in vitro and vivo

Tongue cancer has a very high incidence in China, and there is a need to develop new anti-tumour drugs against it. We synthesised 31 novel quinoline derivatives to test their anti-tumour activity. A compound referred to as “f25” was identified through screening for its high in vitro toxicity against an oral squamous carcinoma cell line (CAL-27). f25 exhibited significant cytotoxicity against CAL-27 cells (IC50 = 7.70 ± 0.58 μΜ). f25 also inhibited the migration and invasion of CAL-27 cells to a level comparable with that of the chemotherapy agent cisplatin. Moreover, f25 promoted the apoptosis of CAL-27 cells. Transcriptome sequencing and western blotting showed that the mechanism of action of f25 against CAL-27 cells involved the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Specifically, f25 could bind to PPAR-α, PPAR-β, and PPAR-γ and increase their expression. In vivo experiments showed that treatment with f25 led to a reduction in tumour volume in nude mice without significant toxicity. Overall, this study highlights the potential of quinoline compounds (particularly f25) for the design and synthesis of anti-tumour drugs. It also underscores the importance of the PPAR signalling pathway as a target for potential cancer therapies.

Ligand-Based Design of Novel Quinoline Derivatives as Potential Anticancer Agents: An In-Silico Virtual Screening Approach.

In this study, using the Comparative Molecular Field Analysis (CoMFA) approach, the structure-activity relationship of 33 small quinoline-based compounds with biological anti-gastric cancer activity in vitro was analyzed in 3D space. Once the 3D geometric and energy structure of the target chemical library has been optimized and their steric and electrostatic molecular field descriptions computed, the ideal 3D-QSAR model is generated and matched using the Partial Least Squares regression (PLS) algorithm. The accuracy, statistical precision, and predictive power of the developed 3D-QSAR model were confirmed by a range of internal and external validations, which were interpreted by robust correlation coefficients (RTrain2=0.931; Qcv2=0.625; RTest2=0.875). After carefully analyzing the contour maps produced by the trained 3D-QSAR model, it was discovered that certain structural characteristics are beneficial for enhancing the anti-gastric cancer properties of Quinoline derivatives. Based on this information, a total of five new quinoline compounds were developed, with their biological activity improved and their drug-like bioavailability measured using POM calculations. To further explore the potential of these compounds, molecular docking and molecular dynamics simulations were performed in an aqueous environment for 100 nanoseconds, specifically targeting serine/threonine protein kinase. Overall, the new findings of this study can serve as a starting point for further experiments with a view to the identification and design of a potential next-generation drug for target therapy against cancer.

Amine Basicity of Quinoline ATP Synthase Inhibitors Drives Antibacterial Activity against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA), a Gram-negative pathogen, is a common cause of nosocomial infections, especially in immunocompromised and cystic fibrosis patients. PA is intrinsically resistant to many currently prescribed antibiotics due to its tightly packed, anionic lipopolysaccharide outer membrane, efflux pumps, and ability to form biofilms. PA can acquire additional resistance through mutation and horizontal gene transfer. PA ATP synthase is an attractive target for antibiotic development because it is essential for cell survival even under fermentation conditions. Previously, we developed two lead quinoline compounds that were capable of selectively inhibiting PA ATP synthase and acting as antibacterial agents against multidrug-resistant PA. Herein we conduct a structure-activity relationship analysis of the lead compounds through the synthesis and evaluation of 18 quinoline derivatives. These compounds function as new antibacterial agents while providing insight into the balance of physical properties needed to promote cellular entry while maintaining PA ATP synthase inhibition.

Highly dispersed palladium nano-catalyst anchored on N-doped nanoporous carbon microspheres derived from chitosan for efficient and stable hydrogenation of quinoline

Under the background of green chemistry, the synthesis of N-heterocycles using efficient, stable and long-life catalysts has still faced great challenges. Herein, we used biomass resource chitosan to fabricate a nanoporous chitosan carbon microsphere (CCM), and successfully designed a stable and efficient Pd nano-catalyst (CCM/Pd). Various physicochemical characterizations provided convincible evidences that the palladium nanoparticles (NPs) were tightly and evenly dispersed on the CCM with a mean diameter of 2.28 nm based on the nanoporous structure and abundant functional N/O groups in CCM. Importantly, the graphitized constructure, the formed defects and larger surface area in CCM were able to promote the immobilization of Pd NPs and the electron transfer between Pd and CCM, thereby significantly improving the catalytic activity. The CCM/Pd catalyst was applied for hydrogenation of quinoline compounds, which showed excellent catalytic activity and durability, as well as good substrate applicability. The application of renewable biomass-based catalysts contributes to the progression of a green/sustainable society.

Antibacterial Activity of Quinoline-Based Derivatives against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa: Design, Synthesis, DFT and Molecular Dynamic Simulations.

Bacterial virulence becomes a significant challenge for clinical treatments, particularly those characterized as Multi-Drug-Resistant (MDR) strains. Therefore, the preparation of new compounds with active moieties could be a successful approach for eradication of MDR strains. For this purpose, newly synthesized quinoline compounds were prepared and tested for their antimicrobial activity against Methicillin-Resistant Staphylococcus Aureus (MRSA) and Pseudomonas Aeruginosa (PA). Among the synthesized derivatives, compounds 1-(quinolin-2-ylamino)pyrrolidine-2,5-dione (8) and 2-(2-((5-methylfuran-2-yl)methylene)hydrazinyl)quinoline (12) were shown to possess the highest antimicrobial activity with the minimum inhibitory concentration with the values of 5±2.2 and10±1.5 μg/mL towards Pseudomonas aeruginosa without any activity towards MRSA. Interestingly, compounds 2-(2-((1H-indol-3-yl)methylene)hydrazinyl)quinoline (13) and 2-(4-bromophenyl)-3-(quinolin-2-ylamino)thiazolidin-4-one (16c) showed significant inhibition activity against Staphylococcus aureus MRSA and Pseudomonas aeruginosa. Compound 13 (with indole moiety) particularly displayed excellent bactericidal activity with low MIC values 20±3.3 and 10±1.5 μg/mL against Staphylococcus aureus MRSA and Pseudomonas aeruginosa, respectively. Effects molecular modelling was used to determine the mode of action for the antimicrobial effect. The stability of complexes formed by docking and target-ligand pairing was evaluated using molecular dynamics simulations. The compounds were also tested for binding affinity to the target protein using MM-PBSA. Density-functional theory (DFT) calculations were also used to investigate the electrochemical properties of various compounds.

Quinolines: A Promising Heterocyclic Scaffold for Cancer Therapeutics.

The quinoline scaffold is a widely recognized heterocycle with applications across various disease categories, ranging from malaria and viral infections to bacterial infections, high cholesterol, and even tumors. Consequently, quinoline plays a crucial role in the development of new drugs, and the field greatly benefits from advancements in computer-aided drug design. This review aims to provide insights into the evolution of quinoline and its derivatives, offering a comprehensive exploration of both marketed and developing drugs. Furthermore, the function and mechanism of quinoline compounds are introduced. Many studies rely on cell experiments to demonstrate drug cytotoxicity. In the concluding section of this review, the interaction between quinoline compounds and targets is simulated using computer-aided drug design methods. A thorough analysis is conducted on the potential influencing factors affecting the binding state between quinoline compounds and targets. Notably, the Pi-Alkyl interaction emerges as a significant contributor, while hydrogen bonding is identified as a pivotal bond in these interactions. This review serves as a valuable overview of the potential contributions of quinoline compounds to cancer treatment. It seamlessly combines the essential functions of marketed quinoline drugs with the promise held by emerging quinoline-based compounds. Additionally, the simulation of interactions between quinoline compounds and proteins through computer-aided design enhances our understanding of these compounds' efficacy.

Quinoline-2-one derivatives as promising antibacterial agents against multidrug-resistant Gram-positive bacterial strains.

This study describes the discovery of a variety of quinoline2-one derivatives with significant antibacterial action vs a spectrum of multidrug-resistant Gram-positive bacterial strains, especially methicillin-resistant Staphylococcus aureus (MRSA). Compounds 6c, 6l, and 6o exhibited significant antibacterial activity versus the Gram-positive bacterial pathogens evaluated. In comparison to the reference daptomycin, compound 6c demonstrated the most effective activity among the assessed derivatives, with MIC concentrations of 0.75 μg/mL versus MRSA and VRE and 2.50 μg/mL against MRSE. We also reported on these compounds' biofilm and dihydrofolate reductase inhibitory activities. Compound 6c showed the greatest antibiofilm action in a dose-dependent way and a substantial decrease of biofilm development in the MRSA ACL51 strain at concentrations of 0.5, 0.25, and 0.12 MIC, with reductions of 79%, 55%, and 38%, consecutively, whereas the corresponding values for vancomycin were 20%, 12%, and 9%. These findings imply that these quinoline compounds could be used to develop a new category of antibiotic representatives to prevent Gram-positive drug-resistant bacterial strains.

Extractive denitrogenization of liquid model fuel using polyethylene glycol methyl ether 350

AbstractIn the present study, we studied the effectiveness of the water‐soluble polymer polyethylene glycol methyl ether 350 (PEG ME‐350) on the extraction of nitrogen‐containing heterocyclic compounds—quinoline and indole—from n‐hexane. The dependences of the quantitative characteristics of the extraction of N‐compounds on the contact time of the phases, the content of PEG ME‐350 in the n‐hexane–water system, the initial concentration of nitrogen‐containing heterocyclic compounds in the organic phase, and the volumetric ratio of the phases were obtained. It has been established that PEG ME‐350 is an effective extractant in the process of stepwise extraction of quinoline and indole, and the mechanisms of their extraction have also been proposed and proven. The results can be further used in the purification of light hydrocarbon fractions from nitrogen‐containing heterocyclic compounds.

Design and Synthesis of Novel Thieno[3,2-c]quinoline Compounds with Antiproliferative Activity on RET-Dependent Medullary Thyroid Cancer Cells.

RET kinase gain-of-function mutations represent the main cause of the high aggressiveness and invasiveness of medullary thyroid cancer (MTC). The selective inhibition of the RET kinase is a suitable strategy for the treatment of this endocrine neoplasia. Herein, we performed an innovative ligand-based virtual screening protocol using the DRUDITonline web service, focusing on the RET kinase as a biological target. In this process, thieno[3,2-c]quinolines 6a-e and 7a-e were proposed as new potential RET inhibitors. The selected compounds were synthetized by appropriate synthetic strategies, and in vitro evaluation of antiproliferative properties conducted on the particularly aggressive MTC cell line TT(C634R) identified compounds 6a-d as promising anticancer agents, with IC50 values in the micromolar range. Further structure-based computational studies revealed a significant capability of the most active compounds to the complex RET tyrosine kinase domain. The interesting antiproliferative results supported by in silico predictions suggest that these compounds may represent a starting point for the development of a new series of small heterocyclic molecules for the treatment of MTC.

Three-Component Ring-Expansion Reaction of Indoles Leading to Synthesis of Pyrrolo[2,3-c]quinolines.

Herein, we have developed an atom- and step-economic three-component cascade reaction that enables a modular platform for the synthesis of pyrrolo[2,3-c]quinoline compounds through ring-expansion/cyclization by way of novel N1-C2 cleavage of indoles. The metal-free catalytic system exhibits a broad functional group tolerance.

Acid/base-co-catalyzed cyclization of ketones with o-amino-benzylamines: Direct synthesis of quinoline compounds

A novel acid/base-co-catalyzed tandem cyclization of various ketones with o-amino-benzylamines employing molecular oxygen as the clean oxidant has been described. The reaction provides an efficient and general strategy for the construction of fused N-heterocyclic compounds, such as dihydrobenzo[c]acridines, indeno[1,2-b]quinolines, dihydro-5H-benzo[6,7]cyclohepta[1,2-b]- quinolines and quinolones in a single step. The broad scope and the use of oxygen as the sole oxidant make this transformation an attractive approach for the synthesis of the above mentioned scaffolds.

Natural Alkaloid Waltherione F-Derived Hydrazide Compounds Evaluated in an Agricultural Fungicidal Field.

In this project, quinoline and quinolone-containing hydrazide compounds were designed and synthesized by introducing a bioactive hydrazide group into the skeleton of waltherione F. The fungicidal activity revealed that some hydrazide compounds exhibited excellent and broad-spectrum fungicidal activity; especially, compounds E8, E12, and E16 showed more than 90% or even 100% inhibition rates against most pathogens at 50 μg·mL-1. The fungicidal mechanism indicated that compound E8 may affect the normal function of the plasma membrane, further generating changes in the morphology and subcellular structure of mycelia. Simultaneously, Fusarium graminearum may resist the E8-treated stress through the metabolic pathways related to l-glutamate, l-glutamine, and glutathione. Finally, the effect of compound E8 on wheat seedling's growth and the toxicity to zebrafish were accomplished. These results will provide important guidance to discover novel fungicidal lead compounds and explore new targets, which are effective ways to alleviate the increasingly severe drug resistance.

Study of Nitrogen Compound Migration during the Pyrolysis of Longkou Oil Shale with Thermal Bitumen as the Intermediate

Oil shale is an unconventional energy resource with high nitrogen content. In this study, XPS, GC–MS and ESI FT-ICR MS were carried out to investigate the nitrogen compound migration during pyrolysis, with thermal bitumen as the intermediate. The results showed that the yield of thermal bitumen was highest when the reaction temperature was 380 °C. In the process of pyrolysis, amines and some nitrides generate ammonia gas due to the hydrogen transfer process, or they generate low-grade amines, which subsequently dissolve in pyrolysis water due to bond breakage during the pyrolysis process. As determined by GC–MS analyses, the basic components in shale oil are mainly quinoline compounds. Benzocarbazole and dibenzocarbazole compounds, such as C1-benzocarbazoles, C2-benzocarbazoles and C3-benzocarbazoles, were detected via ESI FT-ICR MS in thermal bitumen.

Antidiabetic Activity of Daun Wungu (Graptophyllum pictum L. Griff) Extract via Inhibition Mechanism of TNF-α, IL-6, and IL-8: Molecular Docking and Dynamic Study

Diabetes is caused by many factors such as hyperglycemia conditions, it triggers type 1 and 2 diabetes. Hyperglycemia was triggered by the inhibition of glucose absorption of cells and triggers an increase in ROS, insulin signaling can be disrupted due to high ROS levels, the cycle will repeat and then trigger fat accumulation, increase in proinflammatory cytokines, and exacerbate the disease. Previous studies have explained the benefits of Daun Wungu (Graptophyllum pictum L. Griff) to inhibit the activity of proinflammatory cytokines, but the molecular mechanism has not been identified. Prediction of the molecular mechanism of compound activity from Daun Wungu (Graptophyllum pictum L. Griff) with proinflammatory receptors was carried out using an bioinformatics approach, the methods used were preparation, drug-likeness prediction, docking, molecular interaction, and dynamic simulation. The results showed that quinoline compounds from Daun Wungu (Graptophyllum pictum L. Griff) had more negative binding energy with more stable chemical bonds and were predicted to inhibit the activity of proinflammatory cytokines consisting of TNF-, IL-6, and IL-8 proteins.