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The Pummerer rearrangement is extensively utilized for the preparation of various heterocyclic compounds, as well as for the introduction of functional groups such as carbonyl, hydroxyl, and amino groups into organic molecules. The reaction mechanism typically proceeds through an initial electrophilic attack by Lewis acid or another electrophile on the sulfur atom of the sulfoxide, leading to the formation of a sulfonium intermediate. Subsequent rearrangement of this intermediate results in the migration of an alkyl/aryl group from sulfur to a neighboring carbon atom, accompanied by the expulsion of a leaving group. The Pummerer rearrangement of quinoline derivatives has significant synthetic utility and has been employed in the synthesis of various compounds. It has found applications in the synthesis of natural products, agrochemicals, pharmaceuticals, diversity-oriented synthesis, functional group transformations, and other fine chemicals. Overall, The Pummerer rearrangement of quinoline derivatives offers a versatile tool for the synthesis of complex molecules in medicinal chemistry. [ABSTRACT FROM AUTHOR]

In this study, a series of nineteen 2-arylquinolines and 4-acetamido-2-methyl-1,2,3,4-tetrahydroquinolines 4–22 was prepared using Povarov reaction protocols and their in vitro cytotoxicity was tested against human cancer cell lines, HeLa, PC3, MCF-7, and SKBR-3, compared with human dermis fibroblasts as non-tumor cells. In general, these quinoline derivatives displayed compelling selective anticancer properties. It was found that the 2-arylquinoline derivatives 4–16 displayed a better activity profile against the cell lines evaluated than the 2-acetamido-2-methyl-THQs 17–22. Particularly, C-6 substituted 2-phenylquinolines 4–10 and 2-(3,4-methylenedioxyphenyl)quinolines 11–16 displayed important activities against the evaluated cell lines, highlighting the results obtained generally against PC3 and HeLa. At the same time, MCF-7 and SKBR-3 cells were much less sensitive to them. Quinoline 13 and tetrahydroquinoline 18 showed selective cytotoxicity with IC50 values of 8.3 μM and 13.15 μM, respectively, in cervical epithelial carcinoma, while quinolines 12 and 11 displayed good cytotoxicity with considerable IC50 values (31.37 and 34.34 μM) in prostate sarcoma. All these compounds (except 11) stand out due to their low unspecific cytotoxicity presenting a remarkable selectivity (SI = 36.21–113.08) compared to doxorubicin. According to the ADME profiling, aromatic quinolines 4–16 are more lipophilic molecules (c Log P = 2.23–4.13) than partially saturated THQ compounds 17–22 (cLogP = 1.56–3.02), but all quinoline derivatives are more lipophilic molecules than the doxorubicin drug (cLogP = 0.48). The relationship between the lipophilicity (cLogP) and cytotoxic effects (IC50), especially in HeLa and PC3 cells, the quinolines 4–16 with greater octanol/water partition coefficients showed better IC50 values in HeLa and PC3 cells, contrasting with the THQs 17–22 which displayed lower cLogP values and poor activity. Molecular docking studies of most active quinoline compounds 4,5 and 10–14 against tested cancer cell lines and KDM5A, KDM4B, KDM4A, and HER-2 proteins revealed good correlations between the IC50 values exhibited by these molecules and their binding interaction strength suggesting that they could be promising selective regulators of the KDM proteins. [ABSTRACT FROM AUTHOR]

In this report, we unveil a highly efficient novel protocol for the domino synthesis of 2,4‐disubstituted and 4‐substituted quinoline scaffolds. The developed strategy involves earth‐abundant Fe‐catalyzed, solvent‐controlled, switchable routes for the selective construction of 2,4‐disubstituted and 4‐substituted quinoline frameworks, achieved by using either trifluoroethanol (TFE) or methanol (MeOH) as a solvent. By employing TFE as a solvent in Path A, the alkyne itself serves as a dual synthon through Fe‐catalyzed in situ C(sp)–C(sp) bond cleavage, enabling the synthesis of two important molecules: 2,4‐disubstituted and 4‐substituted quinolines. Later, upon switching the reaction medium from TFE to MeOH for Path‐B, only 4‐substituted quinolines were obtained extensively. In this Path‐B, Fe‐catalyzed oxidation of methanol was observed and here methanol functioned as both a solvent and an environmentally benign carbon source. Both of these strategies were utilized to prepare a broad range of mono‐ and di‐substituted quinoline derivatives. In the application section and for practical utility, the scale‐up studies, along with the photophysical properties of the synthesized quinoline moiety are also demonstrated. [ABSTRACT FROM AUTHOR]

A one‐pot synthetic protocol has been developed using aryl acetic acid as new and alternate surrogate for the synthesis of 4‐aryl imidazoquinoxalines with molecular iodine‐DMSO green catalytic system under classical heating at 100–110 °C. A variety of quinoxaline derivatives containing quinoline are prepared by using this methodology. This new protocol has a potential to tolerate broad substrates, that is, different amines and aryl acetic acids. [ABSTRACT FROM AUTHOR]

A 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. [ABSTRACT FROM AUTHOR]

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 11 (or 13) of isoindolo[2,1‐a]quinoline derivatives is crucial for two‐photon absorption properties. [ABSTRACT FROM AUTHOR]

A quinoline derivative 7-((2-aminoethyl)amino)-5-bromo-6-hydroxy-1-methylquinolin-1-ium-3-sulfonate (QEt) containing quinoline ring, - SO 3 - sulfonate, -OH phenol, and amine groups was synthesized and studied luminescence properties. The aqueous solutions QEt 10µM change luminescence color from green (λem = 490 nm) to yellow (λem = 563 nm) as increasing pH and the intensity at a peak of 563 nm is linearly proportional with pH value in the range of pH = 3,0–4,0. The QEt solution can be used as a chemosensor for Cu2+ with an LOD value at 0.66 μ M . Along with the experiment, the structure, absorption and emission spectra of QEt have been investigated by TD-DFT calculation. The result shows that the absorption band centered at 420 nm is due to the electron transition from HOMO to LUMO (π → π*). The results also help to assign emission band centered at 490 nm is due to the S1 → S0 transition (LUMO → HOMO singlet transition), at 563 nm is due to the T1 → S0 transition (LUMO → HOMO triplet transition). The dependence of the relative intensity of each emission peak on pH, which is experimentally recorded, is explained based on the results of theoretical TD-DFT calculation. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a global health concern, necessitating the continuous search for novel therapeutic agents to combat drug-resistant strains and enhance treatment efficacy. The present study focuses on designing, synthesizing, and exploring quinoline analogues as potential anti-tubercular agents. Quinoline scaffolds like bedaquiline inhibit the ATP synthase enzyme involved in energy production. A diverse library of 19 quinoline derivatives was sys tematically synthesized through rational structural modifications. The quinoline analogues were evaluated for their anti-tubercular activity against Mycobacterium tuberculosis (M.tb). Furthermore, the study delves into the molecular interactions between the synthesized quinoline derivatives and M.tb ATP synthase, shedding light on the underlying mechanisms of their anti-tubercular activity. The initial in-vitro screening revealed that some of the designed molecules were active against M.tb, making them potential candidates for further development. A diverse library of 19 quinoline derivatives was systematically synthesized through rational structural modifications. Molecular docking studies showed to target the ATP synthase protein of Mycobacterium tuberculosis (MtB). The quinoline analogs were found to have good anti-tubercular activity again Mtb. [ABSTRACT FROM AUTHOR]

N-Monosubstituted ethylenediamine derivatives with three methylene-tethered aromatic groups ((ArCH2)2NCH2CH2N(R)CH2Ar (R-ArArAr), where Ar = 2-pyridyl, 2-quinolyl, 1- and 3-isoquinolyl and 2-quinoxalyl; R = methyl, benzyl and phenyl) were utilized as pentadentate ligands for copper(II) complexation. Fifteen mononuclear copper(II) complexes were synthesized and exhibit differences in cyclic voltammetry, absorption spectroscopy and solid state geometries, depending on the aromatic group (Ar) and the substituent on the aliphatic nitrogen atom (R) of the ligand. Compared with the pyridine and isoquinoline complexes, the quinoline and quinoxaline derivatives exhibit distinct Cu(II)/Cu(I) redox potentials and d–d transition absorption wavelengths. Similarly, the phenyl derivatives are different from their methyl and benzyl counterparts. These characteristic trends are discussed in relation to the square-pyramidal/trigonal–bipyramidal structure of the complexes which is perturbed by the location of quinoline moieties in the penta- or hexacoordinate complexes with Jahn–Teller distortion. In addition, the results are compared to the copper(II) complexes with pyridine/quinoline mixed ligands, Ph-Ar1Ar2Ar3 ((Ar1CH2)(Ar2CH2)NCH2CH2N(Ph)CH2Ar3). [ABSTRACT FROM AUTHOR]

The higher prevalence of cancer and the unmet need for antioxidant/anti‐inflammatory chemotherapeutic compounds with little side effect are of utmost importance. In addition, the increased likelihood of failure in clinical trials along with increasing development costs may have diminished the range of choices among newer drugs for clinical use. This has dictated the necessity to seek out novel medications by repurposing as it needs less time, effort, and resources to explore new uses of a current or unsuccessful medication. In this study, we examined the biological activity of 10 potential quinoline derivatives. Given the half‐maximal inhibitory concentration (IC50 value) in lipopolysaccharide (LPS) induced inflammation of RAW264.7 mouse macrophages, all commercial FQs and selected quinolines (quinoline‐4‐carboxlic and quinoline‐3‐carboxylic acids) exerted impressively appreciable anti‐inflammation affinities versus classical NSAID indomethacin without related cytotoxicities in inflamed macrophages. Conversely, all 14 tested compounds lacked antioxidative DPPH radical scavenging capacities as compared to ascorbic acid. Gemifloxacin, considerably unlike markets FQs, indomethacin and quinoline derivatives, exerted exceptional and differential antiproliferation propensities in colorectum SW480, HCT116, and CACO2, pancreatic PANC1, prostate PC3, mammary T47D, lung A375, and melanoma A549 adherent monolayers using the sulforhodamine B colorimetric method versus antineoplastic cisplatin. All quinoline derivatives and gemifloxacin alike, but not levofloxacin, ciprofloxacin, or indomethacin, displayed substantially selective viability reduction affinities in prolonged tumor incubations of cervical HELA and mammary MCF7 cells. Specifically kynurenic acid (hydrate), quinoline‐2‐carboxylic acid, quinoline‐4‐carboxylic acid, quinoline‐3‐carboxylic acid, and 1,2‐dihydro‐2‐oxo‐4‐quinoline carboxylic acids possessed the most remarkable growth inhibition capacities against mammary MCF7 cell line, while quinoline‐2‐carboxylic acid was the only quinoline derivative with significant cytotoxicity on cervical HELA cancer cells. It is highly speculated that chelation with divalent metals via co‐planarity with close proximity of the COOH and the N atom could have the potential molecular mechanism for optimally promising repurposed pharmacologies. Conclusively, this study revealed the considerably profound repurposed duality of cytotoxicity and anti‐inflammation pharmacologies of quinoline derivatives. Activity‐guided structural modifications of the present nuclear scaffolds can be inherently linked to the betterment and enhancement of their repurposed pharmacologies. [ABSTRACT FROM AUTHOR]

We report a convergent synthesis of heteroaryl/aryl-annulated pyridine and quinoline derivatives by a metal-free Povarov reaction. para -Toluene sulfonic acid was used as the catalyst in this reaction, which produced the products in good yields from the corresponding aromatic amines and ethyl vinyl ether. A pyridocoumarin and a pyridopyrimidine product were evaluated for their mosquito larvicidal activity against the third instar larvae of the dengue vector mosquito Aedes aegypti. Examination of morphological changes in the larvae showed damage to the target body part after treatment with both the pyridocoumarin and pyridopyrimidine products at the LC50 concentrations. [ABSTRACT FROM AUTHOR]

Quinoline is one of the most important nitrogen containing heterocycles, being widespread in nature and present in a broad variety of pharmacologically active compounds. Specifically, several quinoline based renowned antimalarial agents have served the mankind for several past decades and showed strong potential applications in other field also. 3‐Formyl‐quinoline is a versatile precursor which can be transformed using several easy methods into a wide range of biologically valuable scaffolds. The exploration of 3‐formyl‐quinolines have gained much more attention to medicinal chemists in the field of drug discovery to design and synthesize new fused/tethered quinolines as potent therapeutical agents. This manuscript summarizes the reports (from 2011 to 2023) which showing the synthetic potential of quinoline‐3‐carbaldehydes. [ABSTRACT FROM AUTHOR]

A regioselective synthesis of 4H‐pyrano[2,3‐b]quinoline derivatives via DABCO‐mediated Knoevenagel condensation/heterocyclization sequence has been executed. In this way some new fused heterocyclic compounds were synthesized from 2‐chloroquinoline‐3‐carbaldehyde as a versatile and efficient synthetic building block. The one‐pot three‐component reaction of 2‐chloroquinoline‐3‐carbaldehyde and diverse cyclic active methylenes for construction of highly substituted quinolines scaffold has been accomplished under mild condition. The strategy included herein shows significant advantages, including a facile process with easy purification, excellent yields, wide applicability, available substrates, and cost‐effective/eco‐friendly solvent and catalyst. [ABSTRACT FROM AUTHOR]

Southern root-knot nematodes are among the most pernicious phytoparasites; they are responsible for substantial yield losses in agricultural crops worldwide. The limited availability of nematicides for the prevention and control of plant-parasitic nematodes necessitates the urgent development of novel nematicides. Natural products have always been a key source for the discovery of pesticides. Waltherione A, an alkaloid, exhibits potent nematocidal activity. In this study, we designed and synthesized a series of quinoline and quinolone derivatives from Waltherione A, leveraging a strategy of structural simplification. Bioassays have revealed that the quinoline derivatives exhibit better activity than quinolone derivatives in terms of both nematocidal and fungicidal activities. Notably, compound D1 demonstrated strong nematocidal activity, with a 72 h LC50 of 23.06 μg/mL, and it effectively controlled the infection of root-knot nematodes on cucumbers. The structure–activity relationship suggests that the quinoline moiety is essential for the nematocidal efficacy of Waltherione A. Additionally, compound D1 exhibited broad-spectrum fungicidal activity, with an EC50 of 2.98 μg/mL against Botrytis cinerea. At a concentration of 200 μg/mL, it significantly inhibited the occurrence of B. cinerea on tomato fruits, with an inhibitory effect of 96.65%, which is slightly better than the positive control (90.30%). [ABSTRACT FROM AUTHOR]

A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a–f and 6a–f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a–h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a–d with organic azides. The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a–f and 6a–f and 1,2,3-triazole derivatives 7a–h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis. Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a–f were shown to be biologically active, and 8-hydroxy-N-methyl-N-(prop-2-yn-1-yl)quinoline-5-sulfonamide (3c) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC50 of 100 µM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity. [ABSTRACT FROM AUTHOR]

Organic inhibitors play a crucial role in the corrosion inhibition process. In this work, the performance of the derivative of quinoline PPMQ against corrosion of carbon steel in the acidic medium HCl 1 M was assessed using electrochemical methods. The findings of the experiments showed that the inhibitor had a strong inhibitory impact on the metal tested in the hydrochloric acid solution. The outcomes of the study displayed that the inhibition efficiency of the tested inhibitor enhanced with its concentrations and remained almost stable during immersion time while decreasing slightly with rising temperature. Electrochemical measurements of this study showed that the corrosion was greatly decreased by the organic inhibitor through a charge transfer mechanism with a high inhibition efficiency of 95.58% at an optimal concentration of 10-2 M at 293 K. While potentiodynamic polarization data reported that the inhibitor was a mixed-type inhibitor. PPMQ was inclined towards the Langmuir adsorption isotherm by spontaneous chemical-physical adsorption on the surface of carbon steel. Additionally, thermodynamic and activation data revealed that this action occurs through an endothermic process. Scanning electron microscopy findings showed that the inhibitor's molecules form a protective layer, which confirms the electrochemical results. [ABSTRACT FROM AUTHOR]

The spread of drug-resistant tuberculosis strains has become a significant economic burden globally. To tackle this challenge, there is a need to develop new drugs that target specific mycobacterial enzymes. Among these enzymes, InhA, which is crucial for the survival of Mycobacterium tuberculosis, is a key target for drug development. Herein, 24 compounds were synthesized by merging 4-carboxyquinoline with triazole motifs. These molecules were then tested for their effectiveness against different strains of tuberculosis, including M. bovis BCG, M. tuberculosis, and M. abscessus. Additionally, their ability to inhibit the InhA enzyme was also evaluated. Several molecules showed potential as inhibitors of M. tuberculosis. Compound 5n displayed the highest efficacy with a MIC value of 12.5 μg/mL. Compounds 5g, 5i, and 5n exhibited inhibitory effects on InhA. Notably, 5n showed significant activity compared to the reference drug Isoniazid. Molecular docking analysis revealed interactions between these molecules and their target enzyme. Additionally, the molecular dynamic simulations confirmed the stability of the complexes formed by quinolinetriazole conjugate 5n with the InhA. Finally, 5n underwent in silico analysis to predict its ADME characteristics. These findings provide promising insights for developing novel small compounds that are safe and effective for the global fight against tuberculosis. [ABSTRACT FROM AUTHOR]

Polymeric room‐temperature phosphorescence (RTP) materials especially multicolor RTP systems hold great promise in concrete applications. A key feature in these applications is a triplet charge transfer transition. Aromatic electron donors and electron acceptors are often essential to ensure persistent RTP. There is much interest in fabricating non‐aromatic charge‐transfer‐mediated RTP materials and it still remains a formidable challenge to achieve color‐tunable RTP via charge transfer. Herein, a charge‐transfer‐mediated RTP material by embedding quinoline derivatives within a non‐aromatic polymer matrix such as polyacrylamide (PAM) or polyvinyl alcohol (PVA) is developed. Through‐space charge transfer (TSCT) is achieved upon alkali‐ or heat treatment to realize a long phosphorescence lifetime of up to 629.90 ms, high phosphorescence quantum yield of up to 20.51%, and a green‐to‐blue afterglow for more than 20 s at room temperature. This color‐tunable RTP emerges from a nonaromatic polymer to single phosphor charge transfer that has rarely been reported before. This finding suggests that an effective and simple approach can deliver new color‐tunable RTP materials for applications including multicolor display, information encryption, and gas detection. [ABSTRACT FROM AUTHOR]

Ferrocenyl conjugated oxazepine/quinoline derivatives were presented through the reaction of hexadehydro-Diels-Alder (HDDA) generated arynes with ferrocenyl oxazolines under mild conditions via ring-expanding or rearrangement processes. Water molecule participated in this unexpected rearrangement process to produce quinoline skeletons, and DFT calculations supported a ring-expanding and intramolecular hydrogen migration process for the formation of oxazepine derivatives. Two variants of this chemistry, expanded the reactivity between ferrocenyl conjugated substances and arynes, further providing an innovative approach for the synthesis of ferrocene derivatives. [ABSTRACT FROM AUTHOR]

A domino reaction comprising four consecutive steps based on the strategy of isomerization of allylic alcohols was developed. This base‐catalyzed protocol provided an approach for constructing polysubstituted quinolines without additional additives. A wide range of di‐ or trisubstituted γ‐aminoaryl allylic alcohols bearing alkyl or (hetero)aryl substituents were transformed to a range of structurally diverse quinolines. The utility of this transformation was demonstrated by the application in the concise synthesis of several polysubstituted quinoline derivatives, including natural products and pharmacological agents. Preliminary mechanistic experiments suggest that the isomerization of γ‐aminoaryl allylic alcohol proceeds via an intramolecular 1,3‐hydrogen shift whereas for the aromatization of the dihydroquinoline intermediate two possible pathways exist: acceptorless dehydrogenation and transfer hydrogenation. [ABSTRACT FROM AUTHOR]

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting‐induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q‐NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP‐RTP) is readily achieved by imparting left‐ or right‐hand helical structure through simply twisting, enabling large‐scale production of chiral Q‐NH2@PVA fiber with dissymmetry factor of 10−2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA‐based fibers with outstanding adaptivity in cutting‐edge anti‐counterfeiting technology. [ABSTRACT FROM AUTHOR]

A one‐pot Kabachnik‐Fields reaction is used in the presence of magnesium triflate [Mg(OTf)2] as a catalyst between quinoline, diethyl phosphite (DEP), and substituted aldehydes to synthesize quinoline thioacetohydrazide α‐aminophosphonates (5 a‐f). Analytical and spectroscopic techniques identify the novel compounds. The cytotoxicity properties of the synthesized compounds were examined against HepG2 and MCF7 human cancer cells using the MTT assay. Some of the synthesized compounds exhibit potent anticancer activities. Compounds 5 e and 5 b exhibited the most promising activity against MCF7 human cancer cells, while compounds 5 c and 5 e were potent against HepG2 human cancer cells. Molecular docking experiments on the active compounds showed ring‐stacking interactions between compounds 5 b, 5 c, and 5 e with other proteins, which are compatible with other results. [ABSTRACT FROM AUTHOR]

A novel series of imidazole appended quinoline derivatives (6a–j) have been synthesized using the one-pot three-component reaction that occurred between the starting materials of substituted 2-phenoxyquinolin-3-carbaldehydes (3a-j), benzil (4), and ammonium acetate (5) by taking equimolar ratio. The newly synthesized imidazole-appended quinolines were subjected to probable inhibition against the anti-diabetic drug target maltase enzyme. The efficacy was tested using in-silico molecular docking analysis and molecular dynamics simulation. The studies revealed that the test 6f ligand (3-(4,5-diphenyl-1H-imidazol-2-yl)-2-phenoxy quinoline) is a strong inhibitor of the target protein maltase when compared with the known inhibitor acarbose and sheds new light on the medicinal chemistry research for the application of the synthesized 6f ligand in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Since that hydroquinoline and acridine compounds serve as the fundamental building blocks for the synthesis of many different pharmaceuticals, they are among the most significant classes of chemical compounds that attract the interest of numerous researchers and pharmacologists. Therefore, in this research, The Hantzch reaction was used to prepare these types hydroquinoline and acridine derivatives of compounds, through the reaction of a number substituted benzaldehyde with demidone and α-β diketone substitutes by refluxed with sodium acetate in the presence of iodine and a 1-sulfo-4-(3-(Ferricoxide-Silicondioxide nanopowdertrioxisilyl)propyl) piperazinum-1,4-diphosphate as a catalyst to form 7,7- dimethyl -4,6,7,8-tetrahydroquinoline derivatives which is represented by compounds (1-12) or in the same way by react benzaldehyde substitutes react with demidone and 4-isopropyl cyclohexanone 1-one to form acridin derivatives represented by compounds (13 -17). All product compound are characterized using 1H-NMR spectra and the results confirmed the structures.

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]

The RAF (rapidly accelerated fibrosarcoma) kinases play critical roles in a variety of different cellular processes, including the advancement of the cell cycle, the proliferation of cells, the metabolism of cells, cell migration, and the differentiation of cells. RAF kinase was thus established as an important target for the management of cancer disease. RAF inhibitors have elicited remarkable responses and enhanced survival rates in patients with BRAF‐V600E/K melanoma, but their efficacy is restricted by resistance as a result of mutations in RAF, presenting challenges in the identification of novel RAF inhibitors. This has resulted in the development of two generations of RAF inhibitors. In the past years, a variety of heterocyclic scaffolds that are capable of inhibiting RAF activity have been discovered. Quinoline, a molecule with a fused benzene ring and N‐heterocyclic pyridine, is a prime template for designing a variety of new anticancer drugs. In the last few years, quinoline derivative has been studied for their capability to inhibit RAF kinases. In this review, we have summarized synthesis, biological study, and molecular docking studies of substituted quinoline derivatives, which have shown potent anticancer activity by inhibiting the RAF kinases. The present review would help medicinal chemists streamline and guide their efforts toward developing novel quinoline‐based RAF inhibitors, which will be beneficial for drug development. [ABSTRACT FROM AUTHOR]

We have successfully synthesized quinoline derivatives that exhibit easy scalability and responsiveness to multiple stimuli. These derivatives are capable of forming self-assembled nanoscopic aggregates in an aqueous medium. Consequently, when placed in an aqueous environment, we observe dual fluorescence originating from both twisted intramolecular charge transfer and aggregation-induced emission. The introduction of nerve gas agents, such as diethyl chlorophosphate (DClP) or diethylcyanophosphate (DCNP), to the probe molecules facilitates the charge-transfer process, resulting in a red-shift in absorption maxima. Notably, when operating in fluorescence mode, both of these analytes produce distinct output signals, making them easily distinguishable. DCNP generates a blue fluorescence, while the addition of DClP yields cyan fluorescence. Our mechanistic investigation reveals that the initial step involves phosphorylation of the quinoline nitrogen end. However, in the case of DCNP, the released cyanide ion subsequently attacks the carbonyl carbon centre, forming a cyanohydrin derivative. The response to these target analytes appears to be influenced by the nucleophilicity of the quinoline nitrogen end and the electrophilic nature of the carbonyl unit. [ABSTRACT FROM AUTHOR]

Background: It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. Results: The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1β), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. Conclusion: Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation. [ABSTRACT FROM AUTHOR]

In the present work, novel and effective quinoline-based polybenzoxazines coatings were prepared on cotton fabrics and mild steels to improve the hydrophobic properties and corrosion resistance, respectively. For this purpose, four quinoline containing mono-oxazine-based benzoxazines were synthesized using 8-hydroxyquinoline (Q), and various monoamines, such as: butylamine (ba), hexylamine (ha), octylamine (oa) and aniline (a). The molecular structure of the benzoxazine monomers was verified by 1H-NMR and FTIR spectroscopy. The effect of the aliphatic and aromatic functional groups of the benzoxazines on oxazine ring-opening curing was investigated, and the influence of their corresponding materials on thermal and morphological properties was also elucidated. These quinoline-based monomers have been successfully coated onto the surface: i) cotton fabrics to be used as a water – oil separation method; and ii) mild steel as inhibitor of the corrosion. In this sense, cotton fabric coatings exhibited highly hydrophobic properties (contact angle from 124° to 139°), and subsequently the water oil-separation efficiency was measured to the material that presented the highest contact angle (Poly Q-oa), obtaining a 91% separation efficiency. For benzoxazines coatings on mild steel, impedance tests have indicated that these polymers are corrosion inhibitor effectives. Finally, the antibacterial properties of the quinoline based benzoxazines was also analysed, indicating good antibacterial resistance owing to the existence of long alkyl chains in their respective molecular structure. According to the results obtained from numerous analyses, the quinolone-based polybenzoxazines can be considered as successful materials for applications such as corrosion resistance, oil-water separation, marine coating and microelectronics insulation. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ), a 4-amino quinoline derivative, has antimalarial and anti-inflammatory activity and was most recently proposed in the treatment of SARS-COVID-19. Its pharmacokinetics and toxic side effects necessitate the monitoring of its presence in the environment and its removal from wastewater. In this study, HCQ was removed from an aqueous solution with a removal efficiency of between 80% and 90% under electron beam (EB) irradiation. The degradation of HCQ was propagated by reactions involving both the hydroxyl radical and aqueous electron. The degradation was observed to follow a pseudo-first-order kinetic reaction. The applied radiation dose, pH, and initial HCQ concentration were influential in the degradation efficiency under EB irradiation. Acidic and alkaline pH favored the removal of HCQ under EB irradiation. Even though the initial HCQ was successfully degraded, it was not completely mineralized. The TOC and chemical oxygen demand (COD) remained at a relatively stable level following EB irradiation of the aqueous solutions. This is attributed to the formation of other organic compounds that were not degraded under the investigated experimental conditions. [ABSTRACT FROM AUTHOR]

This review discusses the synthetic pathways of an important class of quinolines known as pyrimido[4,5‐b]quinoline. Due to their profound range as biologically active compounds, they attracted the attention of medical/organic researchers. The construction of pyrimido[4,5‐b]quinolines involved the intermolecular cyclization of diamino chloropyrimidine carbaldehyde and intramolecular cyclization of 2‐amino‐3‐cyanotetra/hexahydroquinoline, 2‐aminoquinoline‐3‐carbonitriles, ester or amide. That class of organic compounds was constructed from the reaction between 2‐chloro‐3‐formylquinoline with amidine, urea, and thiourea. Also, barbituric acid and uracil and their analogous play an important role in synthesizing pyrimidoquinolines via multicomponent reaction strategies (MCR). [ABSTRACT FROM AUTHOR]

Three organoplatinum(II) complexes bearing natural aryl­olefin and quinoline derivatives, namely, [4-meth­oxy-5-(2-meth­oxy-2-oxoeth­oxy)-2-(prop-2-en-1-yl)phen­yl](quinolin-8-olato)platinum(II), [Pt(C13H15O4)(C9H6NO)], (I), [4-meth­oxy-5-(2-oxo-2-propoxyeth­oxy)-2-(prop-2-en-1-yl)phen­yl](quinoline-2-carboxy­l­ato)platinum(II), [Pt(C15H19O4)(C10H6NO2)], (II), and chlorido­[4-meth­oxy-5-(2-oxo-2-propoxyeth­oxy)-2-(prop-2-en-1-yl)phen­yl](quinoline)­plat­inum(II), [Pt(C15H19O4)Cl(C9H7N)], (III), were synthesized and structurally characterized by IR and 1H NMR spectroscopy, and by single-crystal X-ray diffraction. The results showed that the cyclo­platinated arylolefin coordinates with PtII via the carbon atom of the phenyl ring and the C=Colefinic group. The deprotonated 8-hy­droxy­quinoline (C9H6NO) and quinoline-2-carb­oxy­lic acid (C10H6NO2) coordinate with the PtII atom via the N and O atoms in complexes (I) and (II) while the quinoline (C9H7N) coordinates via the N atom in (III). Moreover, the coordinating N atom in complexes (I)–(III) is in the cis position compared to the C=Colefinic group. The crystal packing is characterized by C—H⋯π, C—H⋯O [for (II) and (III)], C—H⋯Cl [for (III) and π–π [for (I)] inter­actions. [ABSTRACT FROM AUTHOR]

N‐Heterocyclic compounds, in particular, quinolines and quinazolines are frequently used in medicinal chemistry. Therefore, the direct and clean synthesis of these valuable scaffolds has been a great interest for many years. 2‐Aminobenzyl alcohols as an alternative reactant instead of unstable and expensive 2‐aminobenzaldehydes can be used in the construction of N‐fused heterocycles including quinolines, quinazolines, oxazines, thiazines, selenazines, imidazoles, diazepines, etc. In this review article, we have discussed recent developments in the use of 2‐aminobenzyl alcohols in the synthesis of diverse heterocycles. [ABSTRACT FROM AUTHOR]

Rh-catalyzed three-component C(sp3)/C(sp2)–H activation has been achieved through a two-directing group strategy. This protocol provides a convenient and efficient pathway for the construction of diverse 8-alkyl quinoline derivatives in one-pot. Furthermore, mechanistic studies revealed that the first C–H amidation was significantly faster than the sequential C–H alkylation. [ABSTRACT FROM AUTHOR]

The article introduces a disposable monolithic column mass spectrometry analysis kit for direct whole blood analysis, offering rapid cleaning and protection of samples, proven effective for quantifying procainamide hydrochloride in rat blood. Topics include the synthesis of functional dibenzoullazines, guaiane-type sesquiterpenoid trimers' discovery, and immobilization of triphenylamine for photocatalytic oxidation of thiols to disulfides.

Comprehensive Summary: A mild and practical method for synthesizing fluorinated quinoline derivatives, which have a wide range of applications in pharmaceuticals, materials, and organic synthesis, was described through C—F bond insertion into indoles using CHBr2F. The simple conditions, readily availability of CHBr2F, as well as the versatility of the transformations make this strategy very powerful in synthesizing 3‐fluoroquinoline and 3‐fluoroquinolone. The mechanistic studies reveal that bromofluorocarbene generated in‐situ under basic condition was the key intermediate. [ABSTRACT FROM AUTHOR]

A series of tetrahydroquinoline derivatives were selectively synthesized at room temperature via electrochemical hydrocyanomethylation of quinoline skeletons using acetonitrile as both a hydrogen source and a cyanomethyl precursor. When a bulky substituent was present at the C2 position, hydrogenation of quinoline derivatives dominated. Furthermore, a deuterium labeling experiment revealed that protons were derived from acetonitrile. This method features mild conditions, high efficiency, wide substrate scope, and good functional group tolerance. [ABSTRACT FROM AUTHOR]

A novel electrochemical method is described for the direct oxidative C--N coupling of tetrahydroquinolines and azoles, enabling the synthesis of dihydroquinoline derivatives under mild reaction conditions. In this approach, 2,2,6,6-tetramethylpiperidinooxy (TEMPO) serves as a redox mediator, and NaI not only acts as an electrolyte but also functions as an iodine mediator. The reaction exhibits good functional group tolerance and high atomic economy, resulting in moderate to excellent yields of the desired dihydroquinoline derivatives. Furthermore, by adjusting the reaction conditions, the corresponding quinoline derivatives can also be selectively obtained. [ABSTRACT FROM AUTHOR]

Background: The in vivo assessment of a novel compound is a pivotal step in the development of a new drug. In this study, we selected 1-(2-bromophenyl)-1,11-dihydro-3H-benzo[h]pyrano[3,2-c]quinoline-3,12(2H)-dione (2-BDBPQD), identified as an exemplary α-glucosidase inhibitor in preliminary in vitro assays, for further evaluation in an in vivo anti-diabetic context. Methods: The in vivo anti-diabetic effect of 2-BDBPQD was assessed using a streptozotocin (STZ)-induced diabetic Wistar rat model. Recognizing the relevance of lipid factors in diabetes, we also investigated the impact of this compound on the lipid profile of diabetic Wistar rats. In silico studies, encompassing docking studies and pharmacokinetic predictions of 2-BDBPQD, were conducted. Results: The results obtained indicated a significant reduction in blood glucose levels with 2-BDBPQD treatment compared to acarbose. However, no significant effects on the lipid profile were observed. In silico studies revealed that 2-BDBPQD interacted with key residues in the α-glucosidase active site and exhibited favorable pharmacokinetic properties. Conclusion: In summary, the study demonstrated the in vivo anti-hyperglycemic activity of 2-BDBPQD. Nevertheless, further in vivo evaluations are recommended to comprehensively assess its potential as a new drug for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

A variety of novel pyrimidopyridoquinazoline, pyrazoloquinoline, and thiazoloquinoline derivatives were synthesized starting from 2,5,7-triamino-4-(4-methoxyphenyl)quinoline-3,8-dicarbonitrile under conventional heating. The same products were also prepared under microwave irradiation to improve the yield and time of the reactions. The structures of all newly synthesized compounds were proved by elemental analysis and IR, 1H and 13C NMR spectroscopy and mass spectrometry. The products were screened for their in vitro antimicrobial activity and showed moderate to high activity. They were also evaluated for anticancer activity against the HePG-2, HCT-116, and MCF-7 cell lines. Molecular docking was used to explore the molecular mechanism of the anticancer activity of 6-(4-methoxyphenyl)-3,9-dihydrodipyrazolo[3,4-b:3',4'-h]quinoline-1,5,7-triamine, which showed the highest cytotoxicity against all the test tested cancer cell lines. [ABSTRACT FROM AUTHOR]

The Rutaceae family is one of the most studied plant families due to the large number of alkaloids isolated from them with outstanding biological properties, among them the quinoline-based alkaloids Graveoline 1 and Dubamine 2. The most common methods for the synthesis of alkaloids 1 and 2 and their derivatives involves cycloaddition reactions or metal-catalyzed coupling processes but with some limitations in scope and functionalization of the quinoline moiety. As a continuation of our current studies on the synthesis and chemical transformation of 2-aminochalcones, we are reporting here an efficient metal-free approach for the total synthesis of alkaloids 1 and 2 along with their analogues with structural diversity, through a two-step sequence involving intramolecular cyclization, oxidation/aromatization, N-methylation and oxidative C-C bond processes, starting from dihydroquinolin-4-ones as common precursors for the construction of the structures of both classes of alkaloids. [ABSTRACT FROM AUTHOR]

This work aimed to evaluate the anticancer potential of the novel 5,6,7,8-tetrahydro-4H-chromenes against selected six cancer cell lines together with the prostate cancer cell line PC-3. A novel series of substituted 5,6,7,8-tetrahydro-4H-chromenes were synthesized through feasible synthetic strategy. The synthetic schemes involve firstly the multi-component reactions of dimedone with the aromatic aldehydes and ethyl acetoacetate to produce the 5,6,7,8-tetrahydro-4H-chromenes derivatives. On the other hand, carrying the same reactions using NH4OAc produced the hexahydroquinoline compounds. Anti-proliferative evaluations and inhibitions for all synthesized compounds toward selected cancer cell lines were carried out and the results revealed that many of them exhibited high inhibitions. Morphology of A549 cell line by the effect of compounds 14f and 16c was performed. [ABSTRACT FROM AUTHOR]

In this study, several fused heterocyclic systems involving tetrahydrobenzopyrans 7a-i and tetrahydrobenzopyridines 9a-i were synthesized. The reactions proceed via a multicomponent reaction of different aromatic aldehydes, cyanoacetanilide derivatives, and cyclohexane-1,3-dione. All the produced compounds were tested for their anticancer activity by using six cancer cell lines such as A549, HT-29, MKN-45, U87MG, SMMC- 7721 and H460 utilizing foretinib as the positive control and the standard MTT assay in vitro. The results indicated that many synthesized derivatives were the most potent towards all the cancer cell lines used, six compounds 7e, 7f, 9b, 9d, 9e, and 9g showed the highest potency. The results obtained in this work enhance further investigations in the future. [ABSTRACT FROM AUTHOR]

Research on novel electrocatalysts with high activity, stability, and economic feasibility for oxygen evolution reaction (OER) is important to the wide application of water electrolyzers. Here, two novel quinoline complexes, L-Co and L-Fe, are synthesized and their crystal structure and electrochemical properties are systematically investigated. Electropolymerization using these complexes are successfully carried out on carbon cloth. The copolymer (P–Co–Fe) is active towards OER in 1 M KOH, with 298 mV overpotential to reach 10 mA cm−2 current densities. Kinetic analyses suggest the P–Co–Fe follows both the adsorbate evolution and lattice oxygen evolution mechanistic pathways. Lower Tafel slope value, lower charge transfer resistance and lower apparent activation energy all suggest enhacned intrinsic activity of the P–Co–Fe, which stem from the electron interaction between the Co and Fe moieties. The P–Co–Fe exhibits stability in 1 M KOH over 24 h, with partial decomposition and the formation of oxides/hydroxides. Novel cobalt and iron complexes of thiophene-modified quinoline derivative were electropolymerized for electrocatalysis of OER with superior activity and stability. [Display omitted] • Two novel complexes with quinoline-derivative as ligand are synthesized. • Electropolymerization of these complexes yields metal-containing copolymer. • The copolymer can actively and stable catalyze oxygen evolution in alkali. • Conversion of the copolymer to metal oxides and (oxy)hydroxides occurs. [ABSTRACT FROM AUTHOR]

Dyes based on quinoline and quinoxaline skeletons were designed for application as visible light photoinitiators. The obtained compounds absorb electromagnetic radiation on the border between ultraviolet and visible light, which allows the use of dental lamps as light sources during the initiation of the photopolymerization reaction. Their another desirable feature is the ability to create a long-lived excited state, which enables the chain reaction to proceed through the mechanism of intermolecular electron transfer. In two-component photoinitiating systems, in the presence of an electron donor or a hydrogen atom donor, the synthesized compounds show excellent abilities to photoinitiate the polymerization of acrylates. In control tests, the efficiency of photopolymerization using modified quinoline and quinoxaline derivatives is comparable to that obtained using a typical, commercial photoinitiator for dentistry, camphorquinone. Moreover, the use of the tested compounds requires a small amount of photoinitiator (only 0.04% by weight) to initiate the reaction. The research also showed a significant acceleration of the photopolymerization process and shortening of the reaction time. In practice, this means that the new two-component initiating systems can be used in much lower concentrations without slowing down the speed of obtaining polymer materials. It is worth emphasizing that these two features of the new initiating system allow for cost reduction by reducing financial outlays on both materials (photoinitiators) and electricity. [ABSTRACT FROM AUTHOR]

Quinoline and its derivatives are a family with unique medicinal properties, including antibacterial effects. It was assumed that the four quinoline derivatives 1, 2, 3 and 4 had significant activity against pathogenic bacteria. These compounds were synthesized and characterized by TLC, IR, 1H NMR, and 13C NMR analyses. The biological activity of compounds was determined as inhibition zone (IZ) in mm. For compound 1 IZ was 19 ± 0.22 against Klebsiella pneumoniae, IZ was 18 ± 0.22 against Bacillus subtilis, and IZ was 17 ± 0.22 against Staphylococcus aureus. 2 displayed IZ of 18 ± 0.22 against both Klebsiella pneumoniae and Bacillus subtilis. 3 showed IZ of 17 ± 0.22 against Staphylococcus aureus. 4 displayed IZ of 21 ± 0.22, thus showing a higher inhibitory activity against Escherichia coli, than ciprofloxacin. These results demonstrate the potential of the synthesized compounds to work as antibacterial drugs against these strains by inhibiting or deactivating the target proteins. [ABSTRACT FROM AUTHOR]

Biologically active quinoline-3,4-dihydropyrimidin-2(1H)-one hybrids as novel monastrol analogs, were designed via molecular hybridization and structural modification rational. The synthesis was easily accessible via classical Biginelli reaction in good yields. Investigation of in vitro cytotoxicity was achieved through MTT cell line assay. The results revealed that the target derivatives showed a spectrum of potential cytotoxic effects on HepG-2, HCT-116, MCF-7, and PC3 cell lines, taking 5-FU as a standard antitumor agent. Compounds 7e (R = tert-butoxy) and 7f (R = 2-methylpropyloxy) showed the greatest cytotoxic efficacy among the tested hybrids on the investigated cell lines; in which 7e showed IC50 values range of (11.57 μM - 19.05 μM), while 7f showed IC50 values range (14.16 μM - 19.96 μM), in comparison with the standard 5-FU (IC50 from 5.3 μM to 8.3 μM). The introduced quinoline-3,4-dihydropyrimidin-2(1H)-one hybrids with their readily straightforward structural modification, may serve as a potential cytotoxic antitumor candidate after suitable optimization. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is a re-emerging RNA virus that is known to cause ocular and neurological abnormalities in infants. ZIKV exploits autophagic processes in infected cells to enhance its replication and spread. Thus, autophagy inhibitors have emerged as a potent therapeutic target to combat RNA viruses, with Hydroxychloroquine (HCQ) being one of the most promising candidates. In this study, we synthesized several novel small-molecule quinoline derivatives, assessed their antiviral activity, and determined the underlying molecular mechanisms. Among the nine synthesized analogs, two lead candidates, labeled GL-287 and GL-382, significantly attenuated ZIKV replication in human ocular cells, primarily by inhibiting autophagy. These two compounds surpassed the antiviral efficacy of HCQ and other existing autophagy inhibitors, such as ROC-325, DC661, and GNS561. Moreover, unlike HCQ, these novel analogs did not exhibit cytotoxicity in the ocular cells. Treatment with compounds GL-287 and GL-382 in ZIKV-infected cells increased the abundance of LC3 puncta, indicating the disruption of the autophagic process. Furthermore, compounds GL-287 and GL-382 effectively inhibited the ZIKV-induced innate inflammatory response in ocular cells. Collectively, our study demonstrates the safe and potent antiviral activity of novel autophagy inhibitors against ZIKV.

This work aims to evaluate the antimicrobial activity of some new quinoline derivatives linked to pyrazole derivatives. The target compounds pyrazolylvinylquinoline 11a-g and 12a-g were achieved by the reaction of 2-chloro-6-nitro-3-quinolinecarboxaldehyde (4) with bromotriphenylphosphonylmethylpyrazole derivatives 9a,b to give the new quinoline derivatives 10a,b which in turn reacted with different aryl amines to afford 11a-g and 12a-g. Pyrazole derivatives 9a,b were obtained by the reaction of hydroxymethylpyrazole derivatives 8a,b with triphenylphosphine hydrobromide. Antimicrobial evaluation of the newly synthesized compounds showed that most of the new compounds appeared active toward Gram-positive bacteria more than Gram-negative bacteria. The biological evaluation of compounds 12d-g displayed the highest antimicrobial activity against the tested microorganism strains. Additionally, compounds 12d and 12f showed excellent activity against P. aeruginosa (MIC50 0.019 mg/mL), while compounds 11d, 11f, 12e, and 12g displayed good activity against the same microorganism (MIC50 0.07 mg/mL). On the other hand, most of the new compounds have moderate activity against E. coli. Compounds 12d and 12f showed excellent activity versus C. albicans in vitro antifungal activity (MIC50 0.15 mg/mL) comparing to or slightly lower than that of Fluconazole. Using molecular docking simulations, we evaluated the binding affinities and interactions of four chosen derivatives 12d-g with a target PDB code 3WT0 protein.

This manuscript describes the synthesis of a triazolyl-pyridine-based phosphine, N-((diphenylphosphaneyl)methyl)-N-methyl-6-(1-phenyl-1H-1,2,3-triazol-4-yl)pyridin-2-amine, [2,6-{(PPh2)CH2N(Me)(C5H3N)(C2HN3C6H5)}] (1) (here onwards referred to as PNN) and its cationic and neutral MnI complexes and catalytic applications. The reaction of 1 with Mn(CO)5Br afforded a cationic complex [Mn(CO)3(PNN)]Br (2), which is highly stable in solid state, but in solution it gradually loses one of the CO groups to form a neutral complex [Mn(CO)2(PNN)Br] (3). Complex 2 on treatment with AgBF4 also yielded a cationic complex [Mn(CO)3(PNN)]BF4 (4). These complexes efficiently promoted the synthesis of quinoline derivatives via acceptor-less dehydrogenative coupling of 2-aminobenzyl alcohol and ketones, with complex 3 showing the highest activity with a very low catalyst loading (0.03 mol%) at 110 °C. Complex 3 (0.5 mol%) also showed excellent catalytic activity in the transfer hydrogenation of ketones and aldehydes to form respective secondary and primary alcohols. [ABSTRACT FROM AUTHOR]