Quinoline Derivatives Research Articles

Unveiling the Anti-convulsant Potential of Novel Series of 1,2,4-Triazine- 6H-Indolo[2,3-b]quinoline Derivatives: In Silico Molecular Docking, ADMET, DFT, and Molecular Dynamics Exploration.

Epilepsy is a chronic neurological disorder caused by irregular electrical activity in the brain. To manage this disorder effectively, it is imperative to identify potential pharmacological targets and to understand the pathophysiology of epilepsy in depth. This research aimed to identify promising leads from a library of 1,2,4-triazine-6Hindolo[ 2,3-b]quinoline derivatives and optimize them using in silico and dynamic processes. We used computational studies to examine 1,2,4-Triazine-6H-indolo[2,3-b]quinoline derivatives. Some methods were used to strengthen the stability of binding sites, including Docking, ADMET, IFD, MMGBSA, Density Functional Theory (DFT), and Molecular Dynamics. HRSN24 and HRSN34 exhibited promising pharmacokinetic and pharmacodynamic characteristics compared to standard drugs (Carbamazepine and Phenytoin) and a co-crystal ligand (Diazepam). Both HRSN24 and HRSN34 presented notable Glide Xp docking scores (-4.528 and -4.633 Kcal/mol), IFD scores (-702.22 and -700.3 Kcal/mol), and MMGBSA scores (-45.71 and -14.46 Kcal/mol). HRSN24 was selected for molecular dynamics and DFT analysis. During MD, HRSN24 identified LYS21, GLY22, ASP24, ARG26, VAL53, MET55, and SER308 as the most important amino acid residues for hydrophobic interactions. A DFT computation was performed to determine the physicochemical properties of HRSN24, revealing a total energy of -1362.28 atomic units, a HOMO value of -0.20186, and a LUMO value of -0.01915. Based on computational modelling techniques, an array of 1,2,4-triazine-6H-indolo [2,3-b]quinoline derivatives were evaluated for their anti-convulsant properties. A stable compound within the GABAA receptor was identified by HRSN24, suggesting its affinity as an anti-convulsant.

The Catalysts-Based Synthetic Approaches to Quinolines: A Review.

The most common heterocyclic aromatic molecule with potential uses in industry and medicine is quinoline. Its chemical formula is C9H7N, and it has a distinctive double-ring structure with a pyridine moiety fused with a benzene ring. Various synthetic approaches synthesize quinoline derivatives. These approaches include solvent-free synthetic approach, mechanochemistry, ultrasonic, photolytic synthetic approach, and microwave and catalytic synthetic approaches. One of the important synthetic approaches is a catalyst-based synthetic approach in which different catalysts are used such as silver-based catalysts, titanium-based nanoparticle catalysts, new iridium catalysts, barium-based catalysts, iron-based catalysts, gold-based catalysts, nickel-based catalyst, some metal-based photocatalyst, α-amylase biocatalyst, by using multifunctional metal-organic framework-metal nanoparticle tandem catalyst etc. In the present study, we summarized different catalyst-promoted reactions that have been reported for the synthesis of quinoline. Hopefully, the study will be helpful for the researchers.

Thermodynamics of the Sorption of Quinoline Derivatives, 1,2,3,4-Tetrahydroquinoline and Pyridazino[4,5-c]Quinoline Under Conditions of RP HPLC

Thermodynamics of the Sorption of Quinoline Derivatives, 1,2,3,4-Tetrahydroquinoline and Pyridazino[4,5-c]Quinoline Under Conditions of RP HPLC

Comprehensive construction of biologically active α‐carbolines from synthetic and natural origin

α‐Carboline is an important scaffold present in various synthetic and naturally obtained bioactive compounds possessing a wide range of pharmacological properties. Hence, in the current comprehensive review, we intend to present the main routes to the synthesis of α‐carboline analogs based on various pathways such as pyrrole, benzene, and pyridine ring annulation. The pathways include either or combinations of transition metal‐catalyzed amination/arylation, Graebe‐Ullmann reaction (thermal pyrolysis, photochemical cyclization), Diels‐Alder cycloaddition and condensation reactions, N‐Heterocyclic carbene catalysed reactions, decarboxylative annulation, etc. of substituted benzene, pyridine, quinoline, and indole derivatives in order to compare the potential of synthetic routes of this series and consolidate the development, current status and perspectives for the design of α‐carboline analogs. Various pharmacological and spectroscopy functions of the compounds belonging to this class are summarized herewith. It also discusses the synthesis of functionalized bioactive naturally obtained hetero‐annulated α‐ carbolines.

Gold‐Catalyzed Annulation Between 1‐[2‐(Dimethoxymethyl)phenyl]prop‐2‐yn‐1‐yl Acetates and α‐Diazo Esters or Anilines to Form Substituted Naphthoates and Indeno[1,2‐b]quinoline, Respectively

AbstractThis work describes gold‐catalyzed annulations of 1‐(2‐(dimethoxymethyl)phenyl)‐1‐prop‐2‐yn‐1‐yl acetate substrates with α‐diazo esters and anilines, respectively yielding substituted naphthoates and indeno[1,2‐b]quinoline derivatives. Our mechanistic analysis indicates 1‐methoxy‐2‐carbonyl‐1H‐indenes as their common intermediates. In the formation of naphthoates, α‐diazo ester attacks at gold‐bound intermediate via an SN2 pathway to enable a allylic methoxy substitution. For indeno[1,2‐b]quinoline derivatives, there are two main reactions, including (i) a reversible formation between intermediate and a double amine addition product and (ii) an arylation reaction of intermediate. Species N‐(phenyl((2E)‐1‐(phenylimino)‐1,3‐dihydro‐2H‐inden‐2‐ylidene)methyl)aniline was converted to indeno[1,2‐b]quinoline in the presence of gold catalyst.

Investigation of Novel Quinoline Derivatives Targeting Epidermal Growth Factor Receptors as Anticancer Agents a Computational Approach

Background: Newer chemical entities are created and synthesis has been made feasible by a variety of computer-aided drug design (CAAD) techniques. In addition to facilitating the visualisation of the ligand-target binding process, the application of in silico methodologies and structure-based drug design (SBDD) allows for the prediction of receptor affinities and significant binding pocket locations. Objective: The goal of the current study was to identify new quinoline derivatives by computational methods specially designed to bind the EGFR receptor in the treatment of breast cancer. Materials and Methods: ChemAxon Marvin Sketch 5.11.5 was used to create derivatives of quinolines. The admetSAR online web tools and SwissADME were utilised to forecast the toxicity and pharmacokinetic characteristics of several substances. A multitude of software programmes, such as Autodock 1.1.2, MGL Tools 1.5.6, Procheck, Protparam ExPasy tool, PyMOL, and Biovia Discovery Studio Visualizer v20.1.0.19295 were also employed to ascertain the ligand-receptor interactions between quinoline derivatives and the target receptor (PDB -5GNK). Result: Almost all components were shown to be less hazardous, orally consumable and to have the appropriate pharmacokinetic characteristics based on in silico study. All newly generated derivative compounds have higher docking scores when compared to the widely used medication sorafenib. Conclusion: Interactions with quinoline analogues boost binding energy and the number of Hbonds produced, making them a suitable place to start when creating compounds for further exploration. The quinoline moiety increases its potential as a novel therapy alternative for breast cancer and could facilitate more comprehensive in vivo, in vitro, chemical-based, and pharma studies by medicinal chemists.

In Silico and In Vitro Evaluation of Quinoline Derivatives as Potential Inhibitors of AChE, BACE1, and GSK3β for Neurodegenerative Diseases Treatment.

Neurodegenerative diseases are characterized by the structural and functional loss of neurons, affecting populations worldwide. Enzymes like acetylcholinesterase (AChE), beta-site APP cleaving enzyme-1 (BACE1), and glycogen synthase kinase 3-beta (GSK3β), contribute to their development. This study explores in silico and in vitro assays of quinoline analogues as potential inhibitors of these enzymes. In silico analyses highlighted derivative SQ6 as the most potent inhibitor for all proteins. In vitro assays confirmed that the quinoline derivatives had a modulating action on the three targets. SQ6 showed a significant AChE inhibition of 94.6%. Regarding the inhibition of GSK3β and BACE1, derivatives SQ6-SQ9, with the quinoline linked to the sulfonamide nitrogen, showed inhibition values above 40%. SQ7 and SQ9 were not considered cytotoxic for cell proliferation in human glioblastoma, and SQ6 did not show cytotoxicity at 7.8 and 3.9 µg mL-1. In murine fibroblasts, SQ6 presented a result similar to that observed for cell proliferation in human glioblastoma, while SQ7 and SQ9 were non-cytotoxic below 62.5 µg mL-1. These findings underscore compound SQ6 as the first potential multitarget enzyme inhibitor for treating neurodegenerative diseases.

Potassium Phosphate-Mediated Synthesis of C4-Phosphorylated Quinolines via Cascade Cycloisomerization of Ynones.

A cascade phosphorylation cycloisomerization of readily accessible ynones and diphenylphosphine oxides facilitated by potassium phosphate is described, allowing for the straightforward synthesis of C4-phosphorylated quinoline scaffolds. The formation of a C-P bond and a C-N bond is achieved in a single procedure without the need for pre-assembled quinoline cores prior to phosphorylation. This transformation operates without the requirement for metals or oxidants and exhibits excellent compatibility with various functional groups. Furthermore, antimicrobial activity evaluation demonstrated that the synthesized C4 phosphorylated quinoline derivatives exhibited potent inhibitory activity against Staphylococcus aureus.

Absorption, Fluorescence, and Two-Photon Excitation Ability of 5-o-Tolyl-11 (or 13)-o-tolylisoindolo[2,1-a]quinolines Prepared by Ring-Closing Metathesis and [2+3] Cycloaddition.

We have successfully improved the fluorescence quantum yield of isoindolo[2,1-a]quinoline derivatives by suppressing the rotation of the phenyl groups at positions 5 and 11 (or 13). Additionally, we found that the planarity of these phenyl groups at positions 5 and 13 of isoindolo[2,1-a]quinoline derivatives is crucial for two-photon absorption properties.

Chemistry and Biological Activity of Thieno[3,4-b]quinoline, Thieno[3,4-c] quinolone, Thieno[3,2-g]quinoline and Thieno[2,3-g]quinoline Derivatives: A Review (Part IX)

Abstract: Over the previous decades, thieno-quinoline derivatives have acquired great interest due to their synthetic and biological applications. These reports have been disclosed on Thienoquinoline synthesis such as thieno[3,4-b]quinoline; thieno[3,4-c]quinolone; thieno [3,2-g]quinoline; thieno[2,3- g] quinoline; spiro-thieno[2,3-g]quinoline; benzo[b]thiophen-iso- quinoline derivatives, and therefore in the existent review, we provided an inclusive update on the synthesis of thienoquinolines. Characterization of the preparation methods and reactivity is categorized based on their types of reactions as addition, alkylation, chlorination, acylation, oxidation, reduction, cyclization and cyclo-condensation. Hence, this study will help the researchers to obtain knowledge from the last literature research to conquer their resolve problems in designing new compounds and processes.

Recent Progress in Synthetic Chemistry and Biological Activities of Pyrimido[ 4,5-b] Quinoline Derivatives (Part III)

Abstract: Amongst heterocyclic compounds, quinoline and pyrimidine are advantaged scaffolds that appear as significant assembly motifs for the development of new drug entities. Moreover, quinolinepyrimidine- inspired hybrids have a number of biological characteristics that are known. In addition, many pyrimido[4,5-b]quinoline ring systems (PyQs4,5-b), specifically concerning medicinal chemistry, have been reported over the past decade. The synthesis of (PyQs4,5-b) using barbituric acid, thiobarbituric acid, pyrimidine, and their derivatives is presented in this review. The preparation of PyQs4,5-b was clarified through the following chemical reactions: Friedländer, Vilsmeier-Haack formylation, Hantzsch-like reaction, and one-pot three-component reaction.

Quinoline as a Privileged Structure: A Recent Update on Synthesis and Biological Activities.

Among heterocyclic compounds, quinoline is one of the best ubiquitous heterocyclic rings for medicinal chemistry purposes. Quinoline appears to be a powerful chemical structure to develop new drug entities. The quinoline derivatives own a wide array of biological activities such as anticancer, antimalarial, antimicrobial, anti-inflammatory, anti-leishmanial, etc. Because of the wide spectrum of bioactivities, the scientific communities are still looking for more efficient synthetic routes to form quinoline derivatives. Therefore, the primary focus of this review is to provide a thorough and inclusive, updated report on quinoline analogs that may pave the way for more efficient drug development.

Biowaste‐Mediated Synthesis of CeO₂–TiO₂ Nanoparticles: An Efficient Recoverable Nanocatalyst for the Solvent‐Free Synthesis of Antipyrine Derivatives and Their Biological Evaluation

AbstractA facile, efficient, and environmentally friendly protocol for the solvent‐free synthesis of antipyrine‐ linked quinoline derivatives catalyzed by CeO2–TiO2 nanocatalyst under ultrasonication is developed. Antipyrine derivatives are involved in various synthetic processes and exhibit valuable biological activities, such as antibacterial, anti‐inflammatory, antioxidant, and anticancer properties. Biowaste‐ derived CeO2–TiO2 nanoparticles have been synthesized using outer covering calyx leaves extract of Physalis peruviana fruits and utilized for the construction of biologically important antipyrine derivatives by the multicomponent reaction in short reaction time with excellent yield. The nanocatalyst was characterized by FT‐IR, powder X‐ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and electron dispersion spectroscopy (EDS). The functionalized nanoparticles show excellent reusability without any significant loss in catalytic activity. The hot filtering experiment shows that there is no noticeable leaching or boomerang effect and that the catalysis is heterogeneous in nature. All synthesized compounds underwent screening for antibacterial activity against selected microorganisms, and their antioxidant activity was assessed using DPPH (2,2‐diphenyl‐1‐picrylhydrazyl). Some of the synthesized compounds exhibited promising results in both screenings.

Design and Synthesis of Ester Linked 1,2,3‐Triazole Quinoline Derivatives with Pancreatic β Cells Protective Activity against Oxidative Stress and Endoplasmic Reticulum Stress for Better Management of Type II Diabetes Mellitus

AbstractUnresolved endoplasmic reticulum (ER) stress and oxidative stress lead to the pathogenesis of type II diabetes mellitus (DM). Connecting links between the ER stress and oxidative stress pathways might play an important role in treatment and pathogenesis of diabetes. Here, we used network pharmacology approach to find the target proteins linking the ER stress and oxidative stress pathways. CHOP emerged as a hub protein from our results and was targeted by 16 newly designed and synthesized ester linked 1,2,3‐triazole quinoline derivatives by molecular docking. Drug likeliness prediction studies revealed all compounds as good druggable candidates. Compounds 5b (R = H, R1 = F), 5j (R = CH3, R1 = F), 5m (R = OCH3, R1 = H), and 5n (R = OCH3, R1 = F) were found to have considerable binding energies and active site amino acid interactions with CHOP. We further showed that compounds 5b, 5m, and 5n exhibited low toxicity with more than 50% cell survival and low IC50 values. These were therefore subjected to evaluate their effects on ER stress and oxidative stress. Finally, compound 5n (R = OCH3, R1 = F) was found to alleviate ER stress and is also a good antioxidant. Identification of such targets and compounds effective in improving ER stress and oxidative stress may provide new insights in the development of therapies and management of T2DM.

A Novel Synthesis Route of Phenyl Quinoline from Nitrochalcone with Hydrazine Hydrate in the Presence of Pd/C

Quinoline is widely known to have many biological activities. Therefore, the development of the synthesis method of a quinoline derivative framework is a priority. A phenyl quinoline derivative, 6,7-dimethoxy-2-phenylquinoline Q1, has been successfully synthesized via a novel one-pot reaction that involves reduction, cyclization, and followed by dehydration of nitrochalcone derivate, 3-(4,5-dimethoxy-2-nitrophenyl)-1-phenylprop-2-en-1-one C1. The reaction was carried out using 80 % hydrazine hydrate in the presence of 10% Pd/C as a catalyst in an ethanol medium. Target compound Q1 was afforded in a good yield of 69.18% in a relatively short reaction time of ±2 h.

Solvent Choice during Flow Assembly of Photocross-Linked Single-Chain Nanoparticles and Micelles Affects Cellular Uptake.

Polymeric micelles have widely been used as drug delivery carriers, and recently, single-chain nanoparticles (SCNPs) emerged as potential, smaller-sized, alternatives. In this work, we are comparing both NPs side by side and evaluate their ability to be internalized by breast cancer cells (MCF-7) and macrophages (RAW 264.7). To be able to generate these NPs on demand, the polymers were assembled by flow, followed by the stabilization of the structures by photocross-linking using blue light. The central aim of this work is to evaluate how the type of solvent affects self-assembly and ultimately the structure of the final NP. Therefore, a library of copolymers with different sequences, including block copolymers (AB, ABA, BAB), and statistical copolymers (rAB and rAC) was synthesized using PET-RAFT with A denoting poly(ethylene glycol) methyl ether acrylate (PEGMEA), B as 2-hydroxyethyl acrylate (HEA), and C as 4-hydroxybutyl acrylate (HBA). The polymers were conjugated with a quinoline derivative to enable the formation of cross-linked structures by photocross-linking during flow assembly. Using water as the dispersant for photocross-linking led to the preassembly of these amphiphilic polymers into compact SCNPs and cross-linked micelles, resulting in a quick photoreaction. In contrast, acetonitrile led to fully dissolved polymers but a low rate of the photoreaction. These intramolecularly cross-linked polymers were then placed in water to result in more dynamic micelles and looser SCNPs. Small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and size exclusion chromatography (SEC) coupled with a viscosity detector show that cross-linking in acetonitrile results in better-defined NPs with a shell rich in PEGMEA. Cross-linking in acetonitrile led to NPs with significantly higher cellular uptake. Interestingly, passive transport was identified as the main pathway for the delivery of our NPs on MCF-7 cells, confirmed by the uptake of NPs on cells treated with inhibitors and by red blood cells. This work underscored the importance of the polymer precursor's structure and the choice of solvent during intramolecular cross-linking in determining the drug delivery efficiency and biological behavior of SCNPs.

Pd-Catalyzed Dual C-H Activation/Cyclization: Convergent and Divergent Synthesis of 1-Azahelicenes.

Herein, we report a convergent synthesis of 1-azahelicenes using easily available quinoline derivatives and cyclic diaryliodonium salts as starting materials. This reaction undergoes a palladium-catalyzed dual C-H activation/cyclization process to give facile access to a wide range of 1-aza[5]helicenes and 1-aza[6]helicenes with abundant functional groups (including F, Cl, Br, I, CF3, SeR, SR, and heteroaryl) in moderate to excellent yields, thereby providing new opportunities to fine-tune the properties of the helicene backbone. In addition, the obtained products could be further transformed into helicene-based Lewis base catalysts and redox switch materials easily. Notably, one selected 1-azahelicene shined bright yellow light by aggregation. These features enlarge the chemical space of 1-azahelicenes and inspire further utilization in other areas of research.

Quinoline Synthesis: Nanocatalyzed Green Protocols-An Overview.

Heterocyclic compounds are of great interest in our daily lives. They are widely distributed in nature and are synthesized in laboratories. Heterocycles play an important role in the metabolism of all living cells, including vitamins and coenzyme precursors like thiamine and riboflavin. Furthermore, heterocyclic systems are essential building blocks for creating innovative materials with intriguing electrical, mechanical, and biological properties. Also, more than 85% of all biologically active chemical entities comprise a heterocycle. As a result, heterocycle synthesis piqued researchers' curiosity, and in recent decades, chemists have concentrated more on nitrogen-containing cyclic nuclei in structures. Quinoline and its derivatives exhibit several biological functions, including antimicrobial, anticancer, antimalarial, anti-inflammatory, antihypertensive, and antiasthmatic effects. In addition, over a hundred quinoline-based drugs are available to treat a variety of disorders. Because of its biological importance, researchers developed one-pot synthetic methods employing effective acid/base catalysts (Lewis acids, Brønsted acids, and ionic liquids), reagents, and transition-metal-based catalysts. These methods have some downsides, including longer reaction times, harsher reaction conditions, creation of byproducts, costly catalysts, use of hazardous solvents, an unacceptable economic yield, and catalyst recovery. Researchers' focus has switched to creating environmentally friendly and effective methods for the synthesis of quinoline derivatives as a result of these methodologic shortcomings. Because of its special qualities, the use of nanocatalysts or nanocomposites offers an option for the effective synthesis of quinolines. This review focuses on the published research articles on nanocatalysts to synthesize substituted quinoline derivatives. This review covers all contributions until May 2024, focusing on quinoline ring building and mechanistic issues. With the aid of this review, we anticipate that synthetic chemists will be able to develop more effective methods of synthesizing quinolines.

Catalytic N-Alkylation of (Hetero)Aromatic Amines and Tandem Annulation Reactions.

A general and practical approach for N-alkylation of heteroaromatic amines with heteroaromatic alcohols is always challenging and rarely reported. Here, we designed and synthesized phosphine-free, robust, and efficient N,N-bidentate-Co(II) complexes for a universal N-alkylation of amines strategy. This present catalytic methodology can be applied to a wide range of substrates by varying alcohols, including aryl, aliphatic, acyclic, and cyclic groups, with heteroaromatic amines such as aminopyridine, 2-aminopyrimidine, and aminoquinoline to provide diverse monoalkylated organonitrogen compounds in good to excellent yields (108 examples). In addition, the utility of the developed catalytic protocol was also extended successfully for the dehydrogenative synthesis of biologically important quinoline derivatives (11 examples). Particularly, 8-aminoquinoline reacted differently with tandem N-alkylated-transfer hydrogenative byproduct (N-benzyl-1,2,3,4-tetrahydroquinolin-8-amine) was obtained, revealing the catalytic activity of the complex I. The reaction proceeded under environmentally benign conditions, which liberates water as the sole byproduct. Notably, a concise synthesis of acetylcholinesterase inhibitors (AChEIs) scaffolds as potential cognition enhancers illustrated the utility of the present protocol. Interestingly, various control and deuterium-labeled experiments were performed, suggesting that the reaction proceeds via the borrowing hydrogen pathway.

Design, Synthesis, and Biological Evaluation of Novel Quinoline Derivatives against Phytopathogenic Bacteria Inspired from Natural Quinine Alkaloids.

A series of 2-(trifluoromethyl)-4-hydroxyquinoline derivatives were designed and synthesized with introduction of the antibacterial fragment amino alcohols, and their antibacterial activity against plant phytopathogenic bacteria was evaluated for the development of quinoline bactericides. It is worth noting that compound Qa5 exhibited excellent antibacterial activity in vitro with a minimum inhibitory concentration (MIC) value of 3.12 μg/mL against Xanthomonas oryzae (Xoo). Furthermore, in vivo assays demonstrated that the protective efficacy of Qa5 against rice bacterial blight at 200 μg/mL (33.0%) was superior to that of the commercial agent bismerthiazol (18.3%), while the curative efficacy (35.0%) was comparable to that of bismerthiazol (35.7%). The antibacterial mechanisms of Qa5 indicated that it affected the activity of bacteria by inducing intracellular oxidative damage in Xoo and disrupting the integrity of the bacterial cell membrane. The above results demonstrated that the novel quinoline derivative Qa5 possessed excellent in vitro and in vivo antibacterial activity, indicating its potential as a novel green agricultural antibacterial agent.