Search Results (277)

Background: Leishmania amazonensis, one of the causative agents of cutaneous leishmaniasis, is responsible for a neglected tropical disease affecting nearly one million individuals worldwide. Although clinical treatments are available, their effectiveness is often compromised by high toxicity and limited selectivity. Methods: From a database, 64 chalcone derivatives were studied using Comparative Molecular Similarity Indices Analysis (CoMSIA) and Hansch analysis (2D-QSAR) to construct predictive computational models. Internal and external validation criteria were applied to identify structural determinants associated with antileishmanial activity. Based on these insights, twelve novel quinoline–chalcone hybrids were designed, synthesized, and biologically evaluated against L. amazonensis. Results: The most robust CoMSIA model combined steric and hydrogen-bond acceptor fields (CoMSIA-SA), while Hansch analysis highlighted electronic descriptors—specifically LUMO energy and the global electrophilicity index—as critical for parasite growth inhibition. Guided by these computational findings, a new series of 12 hybrid quinoline–chalcone derivatives (E001–E012) was synthesized through a two-step procedure, achieving overall yields of 43–71%. Biological assays demonstrated that four compounds displayed inhibitory activity comparable to amphotericin B. Furthermore, physicochemical profiling and in silico pharmacokinetic predictions for the most active compounds (E003, E005, E006, and E011) indicated favorable biocompatibility and drug-like properties. Conclusions: These results underscore the value of an integrative computational–experimental approach in the rational design of next-generation L. amazonensis inhibitors, reinforcing chalcone-based scaffolds as promising pharmacophoric frameworks for antileishmanial drug discovery. Full article

The aim of this work was to prepare new heterodimeric molecules containing pharmacophoric fragments of 3-cyanoquinoline/3-aminothieno[2,3-b]pyridine/3-aminothieno[2,3-b]quinoline on one side and phenothiazine on the other. The products were synthesized via selective S-alkylation of readily available 2-thioxo-3-cyanopyridines or -quinolines with N-(chloroacetyl)phenothiazines, followed by base-promoted Thorpe–Ziegler isomerization of the resulting N-[(3-cyanopyridin-2-ylthio)acetyl]phenothiazines. We found that both the S-alkylation and the Thorpe–Ziegler cyclization reactions, when conducted with KOH under heating, were accompanied to a significant extent by a side reaction involving the elimination of phenothiazine. Optimization of the conditions (0–5 °C, anhydrous N,N-dimethylacetamide and NaH or t-BuONa as non-nucleophilic bases) minimized the side reaction and increased the yields of the target heterodimers. The structures of the products were confirmed by IR spectroscopy, ¹H, and ¹³C DEPTQ NMR studies. It was demonstrated that the synthesized 3-aminothieno[2,3-b]pyridines can be acylated with chloroacetyl chloride in hot chloroform. The resulting chloroacetamide derivative reacts with potassium thiocyanate in DMF to form the corresponding 2-iminothiazolidin-4-one; in this process, phenothiazine elimination does not occur, and the Gruner–Gewald rearrangement product was not observed. The structural features and spectral characteristics of the synthesized 2-iminothiazolidin-4-one derivative were investigated by quantum chemical methods at the B3LYP-D4/def2-TZVP level. A range of drug-relevant properties was also evaluated using in silico methods, and ADMET parameters were calculated. A molecular docking study identified a number of potential protein targets for the new heterodimers, indicating the promise of these compounds for the development of novel antitumor agents. Full article

A novel quinoline-containing benzoxazine resin, 8HQ-fa, has been successfully synthesized at room temperature using sustainable raw materials, such as 8-hydroxyquinoline and furfurylamine as the phenol and amine source, respectively. The chemical structure of the hereinafter referred to as quinolinoxazine is fully characterized by Fourier transform infrared spectroscopy (FT-IR), ¹H and ¹³C nuclear magnetic resonance spectroscopy (NMR), as well as by 2D ¹H–¹H nuclear Overhauser effect spectroscopy (NOESY) and ¹H–¹³C heteronuclear multiple quantum correlation (HMQC) NMR. Thermal properties and polymerization behavior of the monomer are studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The resulting polymer is also characterized in terms of its thermal and fire-related properties by DSC, TGA, and microscale combustion calorimetry (MCC). The resulting thermoset, poly(8HQ-fa), presents good thermal stability as evidenced by its T_g (201 °C), T_d5 and T_d10 (307 and 351 °C, respectively), and char yield (42%), and low flammability as determined by the LOI, heat release capacity, and total heat released values (34.3, 143 J/gK, and 10.8 kJ/g, respectively), making it a self-extinguishing thermoset. The combination of properties and advantages in the synthesis of 8HQ-fa, accompanied by a low polymerization temperature, suggests its great potential in the field of high-performance polymers. Full article

To develop efficient and structurally novel anticoagulants, a library of new hybrid molecules—(Z)-1-(2-(4-arylthiazol-2-yl)hydrazineylidene)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ones—was designed and synthesized through a two-step approach. The reaction of pyrrolo[3,2,1-ij]quinoline-1,2-diones with thiosemicarbazide produced thiosemicarbazones, which were subsequently reacted with α-bromoacetophenones. The structure of the resulting compounds was determined by HPLC-HRMS-ESI analysis, ¹H NMR spectroscopy, and ¹³C NMR spectroscopy. X-ray diffraction analysis unambiguously confirmed the structure of the resulting substances. The synthesized compounds were tested for their anticoagulant activity in vitro. Among the tested derivatives, two substances have a dual effect and exhibit 98–100% inhibitory ability against blood coagulation factors Xa and XIa at 30 μM. IC₅₀ values were also evaluated for these compounds. The results obtained show the high potential of the synthesized derivatives in the development of new multitarget anticoagulant drugs. The docking studies confirmed the experimental results. Full article

The present study reports the sono-chemical synthesis of novel nanosized Cr(III), Mn(II), and Pd(II) complexes incorporating the chloro-2-(quinolin-8-yliminomethyl)-phenol imine ligand. The synthesized complexes were characterized using various spectroscopic and analytical techniques, including Fourier-transform infrared (FT-IR) spectroscopy, ultraviolet–visible (UV–Vis) spectroscopy, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA). The results confirmed the successful coordination of the ligand-to-metal centers, forming stable nanosized metal complexes with distinct physicochemical properties. Biological evaluations, including antimicrobial and antioxidant assays, revealed that the synthesized complexes exhibited enhanced biological activity compared to the free ligand, demonstrating potent antibacterial and antifungal properties against various pathogenic strains. The potential of the complexes to serve as efficient free-radical inhibitors was determined by employing DPPH radical scavenging assays, which underscored their significant antioxidant properties. Furthermore, molecular docking studies were conducted to elucidate the binding interactions of the metal complexes with biological targets, providing insights into their mechanism of action. The findings suggest that the synthesized nanosized Cr(III), Mn(II), and Pd(II) complexes possess promising biological properties, making them potential candidates for pharmaceutical and biomedical applications. The study also demonstrates the effectiveness of sono-chemical synthesis in producing nanosized metal complexes with enhanced physicochemical and biological characteristics. Full article

We report here two new series of designed PDE4 inhibitors, the first one showing the quinoline scaffold recently investigated by us through a fragment-based drug design strategy, and the second consisting of pyrazolo [1′,5′:1,6]pyrimido[4,5-d]pyridazine derivatives. Both the new series were subjected to biological studies to assess their inhibitory effect on PDE4 enzymes, supported by molecular modelling experiments, to rationalize the different activities recorded in the in vitro tests. Interesting results were achieved for two compounds belonging to the tricyclic series, namely 10a and 10e, exhibiting IC₅₀ = 62 and 175.5 nM, respectively. These results could represent the starting point for further studies with the aim of developing new and effective PDE4 inhibitors for biomedical investigations. Full article

Application of organic ligand 2-(3-ethyl-pyrazin-2-yl)quinoline-4-carboxylate with N/O donor atoms enabled solvothermal synthesis of a 2D Cu(II) coordination polymer, {Cu(L)BF₄}_n (L = deprotonated 2-(3-ethyl-pyrazin-2-yl)quinoline-4-carboxylate). Both the ligand and its coordination polymer have been characterized. The condensed ring system of the applied ligand promotes the formation of coordination polymers rather than mononuclear species. The obtained 2D coordination polymer is photoluminescent with bathochromic/hypsochromic shifts in ligand absorption bands leading to a single absorption band at 465 nm. Density Functional Theory was employed to provide a theoretical description of the possible conformational changes within the ligand, with emphasis on the difference between the ligand conformation in its hydrochloride salt and in the polymer. Two models of polymer fragments were constructed to describe the electronic structure and non-covalent interactions. The Quantum Theory of Atoms in Molecules (QTAIM) was applied for this purpose. Using the obtained results, we were able to develop potential energy profiles for various conformations of the ligand. For the set of the studied systems, we detected non-covalent interactions, which are responsible for the spatial conformation. Concerning the models of polymers, electron spin density distribution has been visualized and discussed. Full article

The fibrillary aggregation of α-synuclein is a hallmark of Parkinson’s disease (PD) and a potential target for diagnostics and therapeutics. Although substantial effort has been devoted to the development of positron emission tomography (PET) probes for detecting α-synuclein aggregates, no clinically suitable tracer has been reported. The design and synthesis of 43 new N-(6-methoxypyridin-3-yl)quinolin-2-amine derivatives and an evaluation of their α-synuclein binding affinity is reported here. Compounds 7f, 7j, and 8i exhibited high affinity for α-synuclein and were selected for ¹¹C, ¹⁸F, ¹²⁵I, or ³H radiolabeling. A photoaffinity variant, TZ-CLX, structurally related to 7j and 8i, demonstrated preferential binding to the C-terminal region of α-synuclein fibrils. PET brain imaging studies using [¹¹C]7f, [¹⁸F]7j, and [¹¹C]8i in non-human primates indicated that these three α-synuclein PET tracers penetrated the blood–brain barrier. Both [¹¹C]7f and [¹⁸F]7j showed more favorable brain washout pharmacokinetics than [¹¹C]8i. In vitro binding assays showed that [¹²⁵I]8i is a very potent α-synuclein radioligand, with K_d values of 5 nM for both PD brain tissues and LBD-amplified fibrils; it is also selective for PD tissues versus AD or control tissues. These results strongly suggest that the PET probes based on the N-(6-methoxypyridin-3-yl)quinoline-2-amine scaffold have potential utility in detecting α-synuclein aggregates in vivo. Full article

Searching for new and efficient transfer hydrogenation catalysts, a series of new organometallic ruthenium(II)-arene complexes of the formulae [Ru(η⁶-p-cymene)(L)Cl][PF₆] (1–8) and [Ru(η⁶-p-cymene)(L)Cl][Ru(η⁶-p-cymene)Cl₃] (9–11) were synthesized and fully characterized. These were prepared from the reaction of pyridine–quinoline and biquinoline-based ligands (L) with [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂, in 1:2 and 1:1, metal (M) to ligand (L) molar ratios. Characterization includes a combination of spectroscopic methods (FT-IR, UV-Vis, multi nuclear NMR), elemental analysis and single-crystal X-ray crystallography. The pyridine–quinoline organic entities encountered, were prepared in high yield either via the thermal decarboxylation of the carboxylic acid congeners, namely 2,2′-pyridyl-quinoline-4-carboxylic acid (pqca), 8-methyl-2,2′-pyridyl-quinoline-4-carboxylic acid (8-Mepqca), 6′-methyl-2,2′-pyridyl-quinoline-4-carboxylic acid (6′-Mepqca) and 8,6′-dimethyl-2,2′-pyridyl-quinoline-4-carboxylic acid (8,6′-Me₂pqca), affording the desired ligands pq, 8-Mepq, 6′-Mepq and 8,6′-Me₂pq, or by the classical Friedländer condensation, to yield 4,6′-dimethyl-2,2′-pyridyl-quinoline (4,6′-Me₂pq) and 4-methyl-2,2′-pyridyl-quinoline (4-Mepq), respectively. The solid-state structures of complexes 1–4, 6, 8 and 9 were determined showing a distorted octahedral coordination geometry. The unit cell of 3 contains two independent molecules (Ru-3), (Ru′-3) in a 1:1 ratio, due to a slight rotation of the arene ring. All complexes catalyze the transfer hydrogenation of acetophenone, using 2-propanol as a hydrogen donor in the presence of KOiPr. Among them, complexes 1 and 5 bearing methyl groups at the 8 and 4 position of the quinoline moiety, convert acetophenone to 1-phenylethanol quantitatively, within approximately 10 min with final TOFs of 1600 h⁻¹. The catalytic performance of complexes 1–11, towards the transfer hydrogenation of p-substituted acetophenone derivatives and benzophenone, ranges from moderate to excellent. An inner-sphere mechanism has been suggested based on the detection of ruthenium(II) hydride species. Full article

Heteroaromatic motifs are prevalent in natural products and numerous high-value drug molecules. Consequently, the construction of alkylated heterocyclic frameworks holds significant importance. The Minisci reaction of heteroarenes has evolved into a flexible technique for the synthesis of substituted heterocyclic derivatives. However, the use of strong oxidants and external acid is inevitable during the reaction process. Herein, we present a versatile and accessible method for achieving cross dehydrogenation coupling between quinoline derivatives and inactive ether. This strategy utilizes inexpensive NaI and PPh₃ to support the reaction, obviating the need for metal complexes or sacrificial oxidants, and enables the straightforward synthesis of a diverse library of alkyl-substituted N-heteroarenes. Additionally, radical trapping experiments and fluorescence quenching experiments have been conducted to gain a more comprehensive understanding of the reaction mechanism. Full article

A series of water-soluble molecules based on 8-isopropyl-2-methyl-5-nitroquinoline and 1,10-phenanthroline core were designed by introducing a π-conjugated bridge, vinyl unit –CH=CH–. We present the selective conversion of methyl groups located on the C2 and C9 positions in the constitution of selected quinoline or 1,10-phenanthroline derivatives, respectively, into vinyl (or styryl) products by applying Perkin condensation. The two groups of ligands differ in the presence of one or two arms. The structure of the molecule ((1E,1′E)-(1,10-phenanthroline-2,9-diyl)bis(ethene-2,1-diyl))bis(benzene-4,1,3-triyl) tetraacetate was determined by single-crystal X-ray diffraction measurements. The X-ray, NMR, and DFT computational studies indicate the influence of rotation (rotamers) on the physical properties of studied styryl molecules. The results show that the styryl molecules with the vinyl unit –CH=CH– exhibit significant static and dynamic hyperpolarizabilities. Quantum chemical calculations using density functional theory and B3LYP/6-311++G(d,p) with Grimme’s dispersion correction approach predict the existence and relative stability of different spatial cis(Z)- and trans(E)-conformers of styryl derivatives of quinoline and 1,10-phenanthroline, which exhibit different electronic distribution and conjugation within the molecular skeleton, dipole moments, and steric interactions, leading to variations in their photophysical behavior and various applications. Our studies indicate that the rotation and isomerization of aryl groups can significantly influence the electronic and optical properties of π-conjugated systems, such as vinyl units (–CH=CH–). The rotation of aryl groups around the single bond that connects them to the vinyl unit can lead to changes in the effective π-conjugation between the aryl group and the rest of the π-conjugated system. The rotation and isomerization of aryl groups in π-conjugated systems significantly impact their electronic and optical properties. These changes can modify the efficiency of π-conjugation, affecting charge transfer processes, absorption properties, light emission, and electrical conductivity. In designing optoelectronic materials, such as organic dyes, organic semiconductors, or electrochromic materials, controlling the rotation and isomerization of aryl groups can be crucial for optimizing their functionality. Full article

Aromathecin compounds—which contain the same indolizine core structure as camptothecin-like compounds—are expected to show anticancer activity. Among them, 22-hydroxyacuminatine—which has a substituent on the E-ring of the pentacyclic scaffold—exhibits topoisomerase 1 inhibitory activity; therefore, the development of efficient methods for its synthesis has been actively pursued. Herein, we report a versatile synthetic methodology for introducing various substituents on the E-ring, leading to the total synthesis of 22-hydroxyacuminatine as a model compound of the aromathecin family. The synthesis comprises the following key steps: the synthesis of an isoquinoline N-oxide via the thermal cyclization of 2-alkynylbenzaldehyde oxime, the subsequent Reissert–Henze-type reaction to yield an isoquinolone, and the construction of the indolizine moiety (CD-ring) through C–N bond formation via the Mitsunobu reaction. Consequently, a pentacyclic benz[6,7]indolizino[1,2-b]quinolin-11(13H)-one framework is obtained. Using this methodology, the total synthesis of the natural products norketoyobyrine and naucleficine and an intermediate of the latter, which are indoloquinolizidine-type alkaloids, was achieved, and their antiproliferative activity against HCT-116 human colon cancer cells and HepG2 human liver cancer cells was assessed. Naucleficine and its intermediate exhibited moderate antiproliferative activity against HCT-116 cells, with IC₅₀ values of 55.58 and 41.40 μM, respectively. Full article

We report the synthesis of pyrrolo[3′,2′:3,4]fluoreno[9,1-gh]quinoline and pyrrolo[2′,3′,4′:4,10]anthra[1,9-fg]quinoline derivatives. This novel class of N-doped polycyclic heteroaromatic compounds was synthesized by a site-selective cross-coupling reaction followed by acid-mediated cycloisomerization and Pd-catalyzed CH arylation as the final ring-closing reactions. Preliminary optical and aromatic properties were studied by means of steady-state absorption and fluorescence spectroscopy and DFT calculation. Special emphasis was placed on the impact of ring alternation and position of the N-doping within the scaffold. Full article

Over the past two decades, the copper(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC), commonly known as click chemistry, and C–H bond activation have gained significant attention and have emerged as key synthetic methodologies. In our efforts to synthesize fused nitrogen-containing heterocycles, we developed a palladium-catalyzed protocol for the synthesis of functionalized 7,10-dihydropyrrolo[3,2,1-ij][1,2,3]triazolo[4,5-c]quinolines and 5,8-dihydrobenzo[3,4][1,2,3]triazolo[4′,5′:5,6]azepino[1,2-a]indoles from suitable bromo-substituted N-propargyl-indoles. The reaction conditions demonstrate broad functional group compatibility including halogen, alkoxyl, cyano, ketone, and ester, affording the target compounds in good to high yields. Full article

HIV/AIDS and Mycobacterial tuberculosis (Mtb) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds 11g (IC₅₀ = 0.388 µM), 11h (IC₅₀ = 0.01032 µM) and 11i (IC₅₀ = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with 11h being 9-fold more active than AZT (IC₅₀ = 0.0909 µM), the reference drug. Furthermore, compound 11h displayed moderate activity, with a MIC₉₀ of 88μM against Mtb’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for 11h, the front runner, is >2472. Molecular docking studies revealed that 11h interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that 11h has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and 11h has the potential for further optimisation as an anti-HIV-1 agent. Full article