Quinoline Ring Research Articles

2,3-Diarylquinoline -Based Iridium (III) Complexes: Synthesis, Photophysical Properties and DFT studies

Phosphorescent transition–metal complexes have received considerable interest in the development of efficient organic light-emitting diodes (OLEDs). Iridium complexes derived from heterocyclic ligands have brought a paradigm shift in the optoelectronic materials. Quinoline-based molecular architectures offer excellent materials for such applications due to their exceptional electronic properties, extended π-conjugation and strong ligand–metal binding. Iridium complexes of 2,3-diaryl quinolines with electron rich and electron deficient substituents were synthesized and their electronic properties were studied. Iridium complexes Ir1 and Ir2 bearing the electron withdrawing (-CF3) and electron donating (–OCH3) groups, respectively at the para position of the 2-phenyl ring of 2,3-diarylquinoline exhibited prominent absorption bands in the UV range. Further, the complex Ir3 with unsubstituted 2,3-diarylquinoline ligand and CF3 containing Ir1 showed intensive red phosphorescence near 603 and 611 nm, respectively due to metal-to-ligand and ligand-to-ligand (MLCT/LLCT) charge transfer characteristics. The photoluminescence (PL) spectra of the Ir4 complex derived from 2-phenylquinoline ligand exhibited a bright yellow phosphorescent emission at 589 nm. An additional C3 aryl group on the quinoline ring resulted in a red shift in the emission wavelength of Ir1 and Ir3 complexes compared to Ir4. The PL spectra of Ir2 on the other hand was weak, and blue-shifted to 489 nm, which can be attributed to a ligand-centered (LC) transition. The complexes showed photoluminescence quantum yield (PLQY) in the range of 0.004 to 0.17 and fluorescence lifetime ranged from 1.5 ns to 399 ns, implying the significant effect of the ligand structure on the properties of the complexes. Photophysical investigation of the complexed affirms these complexes to be potent materials for OLEDs fabrication. Cyclic voltammetry was used to investigate the electrochemical characteristics of Ir1-Ir4 complexes in acetonitrile. All of the complexes Ir1-Ir4 exhibited irreversible oxidation waves at 0.44 V, 0.23 V, 0.25 V, and 0.24 V respectively. Ir1-Ir4 complexes showed a reduction potential at −0.98 V, −0.96 V, −1.02 V and −0.97 V respectively. The DFT calculations were used to explore HOMO-LUMO energies, and NBO characteristics by B3LYP level of theory using ECP type double zeta (DZ) quality basis set LanL2DZ for metal and 6-311G(d) basis sets for non-metal atoms. The theoretical calculations were in significant agreement with the experimental studies of these complexes.

Organocatalytic Atroposelective Construction of Axially Chiral Compounds Containing Benzimidazole and Quinoline Rings.

An organocatalytic atroposelective strategy for the construction of axially chiral compounds containing benzimidazole and quinoline rings is described. The enantioselective heteroannulation reaction of 2-alkynylbenzimidazoles with ortho-aminophenylketones proceeded smoothly in the presence of chiral phosphoric acid to provide axially chiral heterobiaryls with good yields and enantioselectivities. This is the first example of the combination of benzimidazole and quinoline rings at the 2- and 3-positions, respectively, into axially chiral heterobiaryls by this new strategy.

Mycobacterium tuberculosis Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti-Mtb Gyrase Activity.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, 7i and 7m, adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best Mtb inhibitors. DNA gyrase inhibition was shown to be exhibited by both, with QCA 7m illustrating better activity up to a 1 μM test concentration. Finally, a docking model for both compounds with Mtb DNA gyrase was developed, and it showed a good correlation with in vitro results.

Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity

In the present work, we report the synthesis, structural characterization, and computational studies of (E)-N'-((5-nitrofuran-2-yl)methylene)quinoline-8-sulfonohydrazide (QNF) as a potential antimicrobial drug candidate. To design the target molecule, we utilized a molecular hybridization technique that connects two antimicrobial pharmacophores (quinoline and 5-nitrofuran rings) with a sulfonyl hydrazone moiety. QNF was synthesized by the condensation of quinoline-8-sulfonohydrazide with 5-nitrofuran-2-carbaldehyde, and characterized by various spectral techniques including single-crystal X-ray crystallography. QNF was extensively evaluated for its antibacterial and antifungal activity. The inhibition capacity of QNF on Candida albicans filamentation and biofilm formation was further investigated. Biofilm inhibition of QNF against C. albicans was supported by molecular docking studies in the binding site of agglutinin-like sequence 3 (Als3). Drug-like profile of QNF was confirmed by in silico calculation of its significant physicochemical properties. Additionally, the optimized geometrical structure, natural bond orbital calculations, frontier molecular orbital and molecular electrostatic potential analysis of QNF were carried out using the density functional theory method at the B3LYP with 6–31+G(d,p) basis set. The predictions of 1H and 13C NMR chemical shift values were performed using the gauge-independent atomic orbital method. Structural parameters and NMR values obtained experimentally were compared with the calculated values.

Synthesis of Cyclopenta[c]quinolines by Palladium-Catalyzed Cyclization of 3-Bromoindoles with Internal Alkynes via Spirocyclic Cyclopentadiene Intermediates.

A novel method for the construction of a cyclopenta[c]quinoline ring via cyclization of 3-bromoindoles with internal alkynes in the presence of palladium is described. The formation of the cyclopenta[c]quinoline ring is proposed from a double [1,5] carbon sigmatropic rearrangement of the spirocyclic cyclopentadiene intermediate, which is generated in situ from the cyclization of 3-bromoindoles with internal alkynes involving a sequential double alkyne insertion into the carbon-palladium bond and dearomatization of indole. The present studies have developed a novel ring-expansion reaction of the pyrrole ring to pyridine via one carbon insertion into the C2-C3 bond of indoles and provided a simple and distinct route for the construction of tricyclic fused-quinoline derivatives that are not easy to access with conventional methods.

Singlet O2 from Ultraviolet Excitation of the Quinoline-O2 Complex.

We report results from experiments with the quinoline-O2 complex, which was photodissociated using light near 312 nm. Photodissociation resulted in formation of the lowest excited state of oxygen, O2 a 1Δg, which we detected using resonance enhanced multiphoton ionization and velocity map ion imaging. The O2+ ion image allowed for a determination of the center-of-mass translational energy distribution, P(ET), following complex dissociation. We also report results of electronic structure calculations for the quinoline singlet ground state and lowest energy triplet state. From the CCSD/aug-cc-pVDZ//(U)MP2/cc-pVDZ calculations, we determined the lowest energy triplet state to have ππ* electronic character and to be 2.69 eV above the ground state. We also used electronic structure calculations to determine the geometry and binding energy for several quinoline-O2 complexes. The calculations indicated that the most strongly bound complex has a well depth of about 0.11 eV and places the O2 moiety above and approximately parallel to the quinoline ring system. By comparing the experimental P(ET) with the energy for the singlet ground state and the lowest energy triplet state, we concluded that the quinoline product was formed in the lowest energy triplet state. Finally, we found the experimental P(ET) to be in agreement with a Prior translational energy distribution, which suggests a statistical dissociation for the complex.

Structurally Induced Chirality of an Achiral Chromophore on Self-Assembled Nanofibers: A Twist Makes It Chiral.

The surface domains of self-assembled amphiphiles are well-organized and can perform many physical, chemical, and biological functions. Here, we present the significance of chiral surface domains of these self-assemblies in transferring chirality to achiral chromophores. These aspects are probed using l- and d-isomers of alkyl alanine amphiphiles which self-assemble in water as nanofibers, possessing a negative surface charge. When bound on these nanofibers, positively charged cyanine dyes (CY524 and CY600), each having two quinoline rings bridged by conjugated double bonds, show contrasting chiroptical features. Interestingly, CY600 displays a bisignated circular dichroic (CD) signal with mirror-image symmetry, while CY524 is CD silent. Molecular dynamics simulations reveal that the model cylindrical micelles (CM) derived from the two isomers exhibit surface chirality and the chromophores are buried as monomers in mirror-imaged pockets on their surfaces. The monomeric nature of template-bound chromophores and their binding reversibility are established by concentration- and temperature-dependent spectroscopies and calorimetry. On the CM, CY524 displays two equally populated conformers with opposite sense, whereas CY600 is present as two pairs of twisted conformers in each of which one is in excess, due to differences in weak dye-amphiphile hydrogen bonding interactions. Infrared and NMR spectroscopies support these findings. Reduction of electronic conjugation caused by the twist establishes the two quinoline rings as independent entities. On-resonance coupling between the transition dipoles of these units generates bisignated CD signals with mirror-image symmetry. The results presented herein provide insight on the little-known structurally induced chirality of achiral chromophores through transfer of chiral surface information.

High-efficiency degradation of norfloxacin by cathodic micro-arc plasma electrolysis:Optimization of operation parameters and investigation on kinetics

In this work, the norfloxacin antibiotic (NOR) in simulated wastewater solution was rapidly degraded by a novel cathodic micro-arc plasma electrolysis (CMPE) treatment within 20 min. The effects and kinetics of initial pH value of solution, supporting electrolyte, and applied voltage on this NOR degradation process were systematically investigated. The intermediate products are analyzed by a Liquid Chromatograph-Mass Spectrometer (LC-MS), and the possible degradation pathways in the NOR degradation process were proposed. The results obtained showed that the NOR removal efficiency increased with the increase of the initial pH value of the solution. When KCl was employed as the supporting electrolyte instead of KNO3 and K2SO4, the removal efficiency of NOR is the highest. In addition, the removal efficiency is not significantly different at 340 V, 380 V, and 420 V, but it is more beneficial to the removal of chemical oxygen demand (COD) and the increase of average current efficiency (ACE) at 380 V. Furthermore, under the optimized operating parameters for the initial pH value of 9, supporting electrolyte of KCl, and applied voltage of 380 V, the 100 mg/L NOR solution can be completely removed within 10 min, and the energy yield and average current efficiency were 0.385 g (kW⋅h)-1 and 0.118. Further, it is found that the degradation pathways of NOR mainly include the piperazine ring opening, hydroxylation, defluorination, and quinoline ring transformation. Overall, this study provides a high-efficiency and novel technique for the NOR degradation treatment.

Deciphering the toxicity mechanism of haloquinolines on Chlorella pyrenoidosa using QSAR and metabolomics approaches

The hazardous potential of haloquinolines (HQLs) is becoming an issue of great concern due to its wide and long-term usage in many personal care products. We examined the growth inhibition, structure-activity relationship, and toxicity mechanism of 33 HQLs on Chlorella pyrenoidosa using the 72-h algal growth inhibition assay, three-dimensional quantitative structure–activity relationship (3D-QSAR), and metabolomics. We found that the IC50 (half maximal inhibitory concentration) values for 33 compounds ranged from 4.52 to > 150 mg·L−1, most tested compounds were toxic (1 mg·L−1 < IC50 < 10 mg·L−1) or harmful (10 mg·L−1 < IC50 < 100 mg·L−1) for the aquatic ecosystem. Hydrophobic properties of HQLs dominate their toxicity. Halogen atoms with large volume appear at the 2, 3, 4, 5, 6, and 7-positions of the quinoline ring to significantly increase the toxicity. In algal cells, HQLs can block diverse carbohydrates, lipids, and amino acid metabolism pathways, thereby resulting in energy usage, osmotic pressure regulation, membrane integrity, oxidative stress disorder, thus fatally damaging algal cells. Therefore, our results provide insight into the toxicity mechanism and ecological risk of HQLs.

Nucleobase Specific Understanding about the Interaction of Antimalarial Drug Chloroquine with Duplex DNA.

Antimalarial action of a drug is closely associated with the interaction with the parasite's DNA. Hence, in this study, the interaction of an important antimalarial drug, chloroquine (CLQ), has been investigated with six different sequences of DNA having pure adenine (A)-thymine (T) and pure cytosine (C)-guanine (G) as well as mixed nucleobases to achieve the nucleobase level of information in the binding of antimalarial drug with DNA along with binding induced stabilization/destabilization of DNA using different spectroscopic methods and molecular dynamics simulation technique. Further, the experiments have been also performed with 4-amino-7-chloroquinoline (7CLQ), an analogue of CLQ, to understand the role of the quinoline ring and side chain of CLQ in the binding with different sequences of DNA. The binding efficiency of CLQ with any sequence of DNA is higher than 7CLQ suggesting that the presence of charge on CLQ plays a prominent role in DNA binding. The data suggest that the binding of drug as well as induced stabilization of DNA depends significantly on the nature as well as the arrangement of the nucleobases. In general, the binding of CLQ with pure CG DNA is higher than with pure AT DNA; moreover, it prefers an alternate order of CG/AT than continual nucleobases in duplex DNA. CLQ predominately accommodates in the minor groove of AT DNA and prefers to form hydrogen bond mostly with the adenine nucleobase. In contrast to AT DNA, CLQ intrudes into the both major and minor grooves, but it is primarily accommodated into the major groove of CG DNA. CLQ forms a hydrogen bond mainly with guanine in the major groove and cytosine in the minor groove of CG DNA which enhances the binding of CLQ compared to AT DNA as well as induces higher stabilization in CG DNA. The molecular level information obtained about the functional group responsible for the interaction of CLQ as well as the role of chemical nature of nucleobases along with its ordering on the binding of CLQ with DNA may be useful in comprehensive understanding of its action mechanism.

Synthesis and Characterization of 8-Amino-6-Methoxy Quinolinium 2,4-Dinitrophenolate: DFT, Molecular Docking, Antimicrobial, and In Vitro Cytotoxicity Evaluation Studies

Quinoline and its derivatives are well recognized for their anticancer activities and pharmacological properties. In this work, the compound 8-Amino-6-methoxyquinolinium 2,4-dinitrophenolate (8A6MQDNP) was synthesized and characterized using FT-IR, FT-Raman, and UV–Vis spectroscopic techniques. The optimized molecular structure, structural properties, and harmonic vibrational frequencies of the molecule were calculated using the DFT/B3LYP method with a cc-pVTZ basis set using the Gaussian 09 software. The observed and calculated vibrational wavenumbers were assigned and correlated well each other. The UV–Vis spectral analysis reveals the π to π* and n to π* electronic transitions of the molecule. The title molecule’s bioactivity is confirmed by frontier molecular orbital (FMOs) analysis; also the intramolecular charge transfer occurred from the quinoline ring to the dinitrophenol. Molecular electrostatic potential surface analysis verifies the FMOs results. The bioactivity of the molecule was confirmed by the natural bond orbital analysis. The Mulliken atomic charge distribution indicates the molecule’s chemical reactivity. Furthermore, the antibacterial results show that the 8A6MQDNP compound can inhibit the development of the tested bacterial strains, most notably the staphylococcus aureus bacterial strain. In vitro cytotoxicity test demonstrates that the 8A6MQDNP compound suppresses the development of A549 cancer cell lines more than HeLa cancer cell lines. Molecular docking investigation confirms that the title molecule inhibits the function of the epidermal growth factor receptor, which has been associated with lung cancer. As a result, the current study paves the way for the development of novel drugs for the treatment of lung cancer.

Construction of Ag deposited g-C3N4 loaded Co[sbnd]Al LDH ternary composites with aim of pharmaceutical wastewater treatment:Pathways and mechanism for ciprofloxacin degradation

Elimination of pharmaceutical drugs from wastewater through photocatalysis is considered an effective and environment-friendly approach to prevent their introduction into the aquatic environment. We constructed ternary Ag deposited g-C3N4 loaded CoAl layered double hydroxide (LDH) composites through multistep synthesis for wastewater remediation of the pharmaceutical industry. We explored the role of g-C3N4 (CN) and Ag NPs in Ag@CN-LDH heterostructure for improving the photocatalytic performance of LDH. This study revealed that the photoactivity of the ternary composite got significantly affected by the CN and Ag loadings. The visible light-driven ternary composite with 10 wt% of CN and 1 wt% of Ag loadings over LDH exhibited the maximum 97% degradation of commercial ciprofloxacin within 90 min, which was highly superior to that noticed for bare LDH. The improved photocatalytic proficiency was credited to the expanded surface region, quick charge move at the CN-LDH interface, and the Surface Plasmon resonance and electron-accepting capability of Ag NPs. The ternary composite was highly stable and recyclable up to five cycles with less than a 3% fall in degradation efficiency. The LC-MS analysis was performed to determine the intermediates and final products. Three degradation pathways were proposed including the cleavage of the piperazine ring and the decarboxylation of the quinoline ring. A possible mechanism for efficient charge transfer and photocatalytic degradation was proposed based on the band edge positions calculated from valence band XPS spectra, photoluminescence analysis, and scavenging experiments.

Photoinduced Long-Distance Hydrogen-Atom Transfer in Molecules with a 7-Hydroxyquinoline Frame and a Carbaldehyde or Aldoxime Group as the Intramolecular Hydrogen Transporting Crane.

The photochemical properties of monomeric 7-hydroxyquinoline substituted at position 8 with carbaldehyde or aldoxime groups were studied for the molecules isolated in solid Ar low-temperature matrices (at 10 K). It was experimentally demonstrated that upon UV excitation, both carbaldehyde and aldoxime groups act as intramolecular cranes transmitting hydrogen atoms from the hydroxyl group to the remote nitrogen atom of the quinoline ring. Furthermore, in the case of 7-hydroxyquinoline-8-aldoxime (and its derivatives), the second photochemical channel was activated upon UV (λ > 360 nm) excitation. This process involves syn-anti isomerization around the double C═N bond in the aldoxime group. The structures of the reactant hydroxy tautomeric form and the photoproduced isomers of the studied molecules were unequivocally determined by means of IR spectroscopy combined with theoretical predictions of the IR spectra of the candidate structures.

Synthesis of Multifused Pyrrolo[1,2-a]quinoline Systems by Tandem Aza-Michael-Aldol Reactions and Their Application to Molecular Sensing Studies.

Herein, we have presented a weak acid-promoted tandem aza-Michael-aldol strategy for the synthesis of diversely fused pyrrolo[1,2-a]quinoline (tricyclic to pentacyclic scaffolds) by the construction of both pyrrole and quinoline ring in one pot. The described protocol fabricated two C-N bonds and one C-C bond in the pyrrole-quinoline rings which have been sequentially formed under transition-metal-free conditions by the extrusion of eco-friendly water molecules. A ketorolac drug analogue has been synthesized following the current protocol, and one of the synthesized tricyclic pyrrolo[1,2-a]quinoline fluorophores has been used to detect highly toxic picric acid via the fluorescence quenching effect.

Molecular modeling of 3‑chloro-3-phenylquinoline-2,4‑dione, crystal structure and cytotoxic activity for developments in a potential new drug

3-Chloro-3-phenylquinoline-2,4‑dione (2) is an intermediate product in the synthesis of 1-phenyl-2H,6H-imidazo[1,5-c]quinazoline-3,5‑dione (PhIC). PhIC, its intermediates, and derivatives belong to quinolines or quinazolines - heterocyclic compounds with biological activity. However, only compound 2 contains nitrogen and chlorine atoms in the structure and has the most probability of having anticancer properties. In this work, the crystal structure of compound 2 was investigated by X-Ray crystallography and the molecular modeling was made by DFT methods. The cytotoxic activities of 3‑hydroxy-3-phenylquinoline-2,4‑dione, 3‑chloro-3-phenylquinoline-2,4‑dione and 3-amino-3-phenylquinoline-2,4‑dione, respectively compounds 1, 2, and 3 (with quinoline ring), and 2-(2-hydroxypropyl)-6-H-imidazo[1,5-c]quinazoline-3,5‑dione – compound 4 (with imidazoquinoline ring) against the cell lines: mouse fibroblast L929 and human gastric adenocarcinoma cells (AGS) were tested. The crystal structure of compound 2 was established and the intermolecular interactions were described. Only one pair of enantiomers was found in the unit cell, whereas molecular modeling showed two pairs of enantiomers AA’ and BB’ are stable. The enantiomer pairs can transform into each other to better spatial packing in the crystal. Compounds 2 and 4 show high cytotoxic activity against the L929 line at the concentration range 0.05– 50 µg/ml, and AGS cells (0.1– 50 µg/ml). When bound to an appropriate carrier to deliver the compound directly to neoplastic cells, their use as anti-neoplastic substances cannot be excluded.

Vilsmeier-Haack Cyclisation as a Facile Synthetic Route to Thieno [2,3- b] Quinolines (Part I)

Abstract: Quinoline ring system is extensively dispensed in natural products, especially in alkaloids. Moreover, thieno[2,3-b]quinolines have vast biological activities, including urea transporter inhibition, anti-microbial, antitumor, antioxidant, anti-inflammatory, and antiproliferative EGFR tyrosine kinase inhibition. Vilsmeier-Haack is considered the most facile and promising set of synthetic routes, leading to 2-chloro-3-formylquinolines through Vilsmeier-Haack cyclisation of N- arylacetamides, which are subsequently used as key intermediates for the synthesis of thieno[2,3-b]quinolones (Tqs). Many varieties of thieno[2,3-b]quinolines (Tqs) ring systems, specifically concerning medicinal chemistry, have been developed over the past decade. In light of these facts, this review presents a systematic and comprehensive survey of the method of preparation and the chemical reactivity of thieno[2,3-b]quinolines through the Vilsmeier-Haack reaction. In this study, the methods of preparation and the chemical reactivity of (Tqs) by using the Vilsmeier-Haack reaction are discussed. Since the beginning of the 21st century, they have been advancing towards synthesizing substituted Tqs. It can be concluded that substituted Tqs can be used as building blocks for the synthesis of polyfunctionalized heterocyclic compounds with pharmacological interest.

Discriminative 'Turn-on' Detection of Al3+ and Ga3+ Ions as Well as Aspartic Acid by Two Fluorescent Chemosensors.

In this work, two Schiff-base-based chemosensors L1 and L2 containing electron-rich quinoline and anthracene rings were designed. L1 is AIEE active in a MeOH-H2O solvent system while formed aggregates as confirmed by the DLS measurements and fluorescence lifetime studies. The chemosensor L1 was used for the sensitive, selective, and reversible 'turn-on' detection of Al3+ and Ga3+ ions as well as Aspartic Acid (Asp). Chemosensor L2, an isomer of L1, was able to selectively detect Ga3+ ion even in the presence of Al3+ ions and thus was able to discriminate between the two ions. The binding mode of chemosensors with analytes was substantiated through a combination of 1H NMR spectra, mass spectra, and DFT studies. The 'turn-on' nature of fluorescence sensing by the two chemosensors enabled the development of colorimetric detection, filter-paper-based test strips, and polystyrene film-based detection techniques.

Chemistry of 2-(Pipridin-1-yl) and/ or 2-(Morpholin-1-yl) Quinolines (Part II): Synthesis, Reactivity and Biological Activities

Background: Vilsmeier-Haack formylation of N-arylacetamides and used them as a key intermediate for preparation of 2-(piperidin-1-yl) and/ or 2-(morpholin-1-yl) quinoline-3- carbaldehydes. these used as precursors for the synthesis of 2-(piperidin-1-yl) and/ or 2-(morpholin- 1-yl) quinoline derivatives through the reaction with active methyl and/ or methylene component, Claisen-Schmidt condensation, one-pot multicomponent reactions (MCRs), reductive amination, Grignard reaction, etc. Methods: This review demonstrates the synthesis of 2-chloroquinoline-3-carbaldehyde derivatives, through Vilsmeier-Haack formylation of N-arylacetamides that used as a precursor for preparation of 2-(piperidin-1-yl) and/ or 2-(morpholin-1-yl) quinoline- 3-carbaldehydes and reacted them with various reagents to form the 2-(piperidin-1-yl) and/ or 2-(morpholin-1-yl) quinolines derivatives. Results: Many 2-(piperidin-1-yl) and/ or 2-(morpholin-1-yl) quinolines derivatives were achived through the reaction with active methyl and/ or methylene component, Claisen-Schmidt condensation, one-pot multicomponent reactions (MCRs), reductive amination, Grignard reaction, etc…. Conclusion: Many quinoline ring systems, specifically concerning medicinal chemistry, had been published over the past decade. During this review, we have outlined the synthetic routes and reactions of 2-(piperidin-1-yl) and/ or 2-(morpholin-1-yl) quinoline-3-carbaldehydes. This review implies a section of the synthesis of 2-(piperidin-1-yl) and/ or 2-(morpholin-1-yl) quinoline-3-carbaldehydes which can be prepared via Vilsmeier formylation of N-arylacetamides followed by heating of the formed aldehydes with piperidine or morpholine and two sections on its reactions with different reagents were presented. Eventually, this review focus upon 2-(piperidin-1-yl) and/ or 2-(morpholin-1- yl) quinoline-3-carbaldehydes as an interesting heterocyclic compound that can be utilized as a precursor and building block for the synthesis of an extended range of heterocyclic systems which have a potent pharmacological interest.

Ultrasound assisted Cu-catalyzed Ullmann-Goldberg type coupling-cyclization in a single pot: Synthesis and in silico evaluation of 11H-pyrido[2,1-b]quinazolin-11-ones against SARS-CoV-2 RdRp

The in silico evaluation of 11H-pyrido[2,1-b]quinazolin-11-one derivatives against SARS-CoV-2 RdRp was undertaken based on the reports on antiviral activities of this class of compounds in addition to the promising interactions of the antiviral drug penciclovir as well as quinazoline derivatives with SARS-CoV-2 RdRp in silico. The target compounds were prepared via an Ullmann–Goldberg type coupling followed by the subsequent cyclization (involving amidation) in a single pot. The methodology involved a CuI-catalyzed reaction of 2-iodobenzoate ester with 2-aminopyridine or quinolin-2-amine or thiazol-2-amine under ultrasound to give the expected products in acceptable (51–93%) yields. The molecular interactions of the synthesized 11H-pyrido[2,1-b]quinazolin-11-one derivatives with the SARS-CoV-2 RdRp (PDB: 7AAP) were evaluated in silico. The study suggested that though none of these compounds showed interactions better than penciclovir but the compound 3a and 3n appeared to be comparable along with 3b seemed to be nearly comparable to favipiravir and remdesivir. The compound 3n with the best binding energy (-79.85 Kcal/mol) participated in the H-bond interactions through its OMe group with THR556 as well as ARG624 and via the N-5 atom with the residue SER682. The in silico studies further suggested that majority of the compounds interacted with the main cavity of active site pocket whereas 3h and 3o that showed relatively lower binding energies (-66.06 and -66.28 Kcal/mol) interacted with the shallow cavity underneath the active site of SARS CoV-2 RdRp. The study also revealed that a OMe group was favourable for interaction with respect to its position in the order C-8 > C-1 > C-2. Further, the presence of a fused quinoline ring was tolerated whereas a fused thiazole ring decreased the interaction significantly. The in silico predictions of pharmacokinetic properties of 3a, 3b and 3n indicated that besides the BBB (Blood Brain Barrier) penetration potential these molecules may show a good overall ADME. Overall, the regioisomers 3a, 3b and 3n have emerged as molecules of possible interest in the context of targeting COVID-19.

Quinoline Hydrazide/Hydrazone Derivatives: Recent Insights on Antibacterial Activity and Mechanism of Action.

Antibiotics are becoming gradually ineffective due to drug resistance, leading to greater difficulty in the treatment of infectious diseases. Therefore, the development of new chemical entities with different mechanisms of action is essential in the fight against resistant microorganisms. Various studies have shown that quinoline hydrazide/hydrazone derivatives possess several biological activities, such as antimalarial, antitubercular, anticancer, anti-inflammatory, and antimicrobial. Among these activities, the antibacterial activity of quinoline hydrazide/hydrazone derivatives is noteworthy. The synthetic flexibility of the quinoline ring has led to the development of a wide range of structurally diverse quinoline hydrazide/hydrazone derivatives, which can act at various bacterial targets such as DNA gyrase, glucosamine-6-phosphate synthase, enoyl ACP reductase, and 3-ketoacyl ACP reductase. This review emphasizes the antibacterial potential of various reported quinoline hydrazide/hydrazone derivatives based on substitution in the quinoline ring. The antibacterial activity of various metal-quinoline hydrazide/hydrazone complexes is also discussed. The aim of this review is to assemble and scrutinize the latest reports in this promising area of drug development.