Search Results (37)

Background/Objectives: Glioblastoma multiforme (GBM), an aggressive and deadly brain tumour, presents significant challenges in achieving effective treatment due to its resistance to current therapies and poor prognosis. This study aimed to synthesise and evaluate 23 novel analogues of 3,4-dihydroquinolin-2(1H)-one, designed to enhance druggability and solubility, and to investigate their potential as VEGFR2 inhibitors for GBM treatment. Methods: The synthesised compounds were analysed using in silico methods, including molecular docking and dynamics studies, to assess their interactions with key residues within the VEGFR2 binding pocket. In vitro evaluations were performed on U87-MG and U138-MG GBM cell lines using MTT assays to determine the IC50 values of the compounds. Results: Among the tested compounds, 4u (IC50 = 7.96 μM), 4t (IC50 = 10.48 μM), 4m (IC50 = 4.20 μM), and 4q (IC50 = 8.00 μM) demonstrated significant antiproliferative effects against both the U87-MG and U138-MG cell lines. These compounds exhibited markedly higher efficacy compared to temozolomide (TMZ), which showed IC50 values of 92.90 μM and 93.09 μM for U87-MG and U138-MG, respectively. Molecular docking and dynamics studies confirmed strong interactions between the compounds and VEGFR2 kinase, supporting their substantial anti-cancer activity. Conclusions: This study highlights the promising potential of 3,4-dihydroquinolin-2(1H)-one analogues, particularly 4m, 4q, 4t, and 4u, as VEGFR2-targeting therapeutic agents for GBM treatment. Further detailed research is warranted to validate and expand upon these findings. Full article

Dihydroquinolin-2(1H)-ones (DHQOs) represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild, and efficient synthetic methods has been widely considered by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of DHQOs via the catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization, and photochemical cyclization reactions. Additionally, the substrate scope and mechanistic details are also discussed. This paper provides a useful reference for the development of diverse synthesis methodologies of DHQO. Full article

The 2-oxo-1,2-dihydroquinolin-8-yl 4-chlorobenzoate was synthesized in good yield using a triethylamine-mediated O-acylation reaction between 8-hydroxyquinolin-2(1H)-one and 4-chlorobenzoyl chloride in acetonitrile at room temperature. This methodology is notable for its clean reaction profile and straightforward procedure. The 2-oxoquinoline derivative was characterized using spectroscopic, spectrometric, and thermal analyses, enabling a comprehensive understanding of its molecular structure and thermal properties. Full article

H₃R is becoming an attractive and promising target for epilepsy treatment as well as the discovery of antiepileptics. In this work, a series of 6-aminoalkoxy-3,4-dihydroquinolin-2(1H)-ones was prepared to screen their H₃R antagonistic activities and antiseizure effects. The majority of the target compounds displayed a potent H₃R antagonistic activity. Among them, compounds 2a, 2c, 2h, and 4a showed submicromolar H₃R antagonistic activity with an IC₅₀ of 0.52, 0.47, 0.12, and 0.37 μM, respectively. The maximal electroshock seizure (MES) model screened out three compounds (2h, 4a, and 4b) with antiseizure activity. Meanwhile, the pentylenetetrazole (PTZ)-induced seizure test gave a result that no compound can resist the seizures induced by PTZ. Additionally, the anti-MES action of compound 4a fully vanished when it was administrated combined with an H₃R agonist (RAMH). These results showed that the antiseizure role of compound 4a might be achieved by antagonizing the H₃R receptor. The molecular docking of 2h, 4a, and PIT with the H₃R protein predicted their possible binding patterns and gave a presentation that 2h, 4a, and PIT had a similar binding model with H₃R. Full article

The production of active pharmaceutical ingredients (APIs) and fine chemicals is accelerating due to the advent of novel microreactors and new materials for immobilizing customized biocatalysts that permit long-term use in continuous-flow reactors. This work studied the scalability of a tunable U-shape magnetic nanoparticles (MNPs)-based microreactor. The reactor consisted of a polytetrafluoroethylene tube (PTFE) of various inner diameters (ID = 0.75 mm, 1.50 mm, or 2.15 mm) and six movable permanent magnets positioned under the tube to create reaction chambers allowing the fluid reaction mixture to flow through and above the enzyme-loaded MNPs anchored by permanent magnets. The microreactors with various tube sizes and MNP capacities were tested with the preparative scale kinetic resolution of the drug-like alcohols 4-(3,4-dihydroisoquinolin-2(1H)-yl)butan-2-ol (±)-1a and 4-(3,4-dihydroquinolin-1(2H)-yl)butan-2-ol (±)-1b, utilizing Lipase B from Candida antarctica immobilized covalently onto MNPs, leading to highly enantioenriched products [(R)-2a,b and (S)-1a,b]. The results in the U-shape MNP flow reactor were compared with reactions in the batch mode with CaLB-MNPs using similar conditions. Of the three different systems, the one with ID = 1.50 mm showed the best balance between the maximum loading capacity of biocatalysts in the reactor and the most effective cross-section area. The results showed that this U-shaped tubular microreactor might be a simple and flexible instrument for many processes in biocatalysis, providing an easy-to-set-up alternative to existing techniques. Full article

The synthesis of novel fluoroquinolones, congeners of ciprofloxacin, which was inspired by earlier work on spirocyclic ciprofloxacin, is described. An antibacterial evaluation of the 11 fluoroquinolone compounds synthesized against the ESKAPE panel of pathogens in comparison with ciprofloxacin revealed that the more compact spirocycles in the fluoroquinolone periphery resulted in active compounds, while larger congeners gave compounds that displayed no activity at all. In the active cohort, the level of potency was comparable to that of ciprofloxacin. However, the spectrum of antibacterial activity was quite different, as the new compounds showed no activity against Pseudomonas aeruginosa. Among the prepared and tested compounds, the broadest range of activity (five pathogens of the six in the ESKAPE panel) and the highest level of activity were demonstrated by 1-yclopropyl-7-[8-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-6-azaspiro[3.4]oct-6-yl]-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which is the lead compound nominated for further characterization and development. Full article

The DYRK (Dual-specificity tyrosine phosphorylation-regulated kinase) family of protein kinases is involved in the pathogenesis of several neurodegenerative diseases. Among them, the DYRK1A protein kinase is thought to be implicated in Alzheimer’s disease (AD) and Down syndrome, and as such, has emerged as an appealing therapeutic target. DYRKs are a subset of the CMGC (CDK, MAPKK, GSK3 and CLK) group of kinases. Within this group of kinases, the CDC2-like kinases (CLKs), such as CLK1, are closely related to DYRKs and have also sparked great interest as potential therapeutic targets for AD. Based on inhibitors previously described in the literature (namely TG003 and INDY), we report in this work a new class of dihydroquinolines exhibiting inhibitory activities in the nanomolar range on hDYRK1A and hCLK1. Moreover, there is overwhelming evidence that oxidative stress plays an important role in AD. Pleasingly, the most potent dual kinase inhibitor 1p exhibited antioxidant and radical scavenging properties. Finally, drug-likeness and molecular docking studies of this new class of DYRK1A/CLK1 inhibitors are also discussed in this article. Full article

This study showcases the application of an integrated workflow of molecular networking chemical profiling (GNPS), together with miniaturized microbioreactor cultivation profiling (MATRIX) to successfully detect, dereplicate, prioritize, optimize the production, isolate, characterize, and identify a diverse selection of new chemically labile natural products from the Queensland sheep pasture soil-derived fungus Aspergillus sp. CMB-MRF324. More specifically, we report the new tryptamine enamino tripeptide aspergillamides E–F (7–8), dihydroquinoline-2-one aflaquinolones H–I (11–12), and prenylated phenylbutyrolactone aspulvinone Y (14), along with an array of known co-metabolites, including asterriquinones SU5228 (9) and CT5 (10), terrecyclic acid A (13), and aspulvinones N-CR (15), B (16), D (17), and H (18). Structure elucidation was achieved by a combination of detailed spectroscopic and chemical analysis, biosynthetic considerations, and in the case of 11, an X-ray crystallographic analysis. Full article

The enzymatic kinetic resolution (EKR) of racemic alcohols or esters is a broadly recognized methodology for the preparation of these compounds in optically active form. Although EKR approaches have been developed for the enantioselective transesterification of a vast number of secondary alcohols or hydrolysis of their respective esters, to date, there is no report of bio- or chemo-catalytic asymmetric synthesis of non-racemic alcohols possessing 1,2,3,4-tetrahydroquinoline moiety, which are valuable building blocks for the pharmaceutical industry. In this work, the kinetic resolution of a set of racemic 1,2,3,4-tetrahydroquinoline-propan-2-ols was successfully carried out in neat organic solvents (in the case of CAL-B and BCL) or in water (in the case of MsAcT single variants) using immobilized lipases from Candida antarctica type B (CAL-B) and Burkholderia cepacia (BCL) or engineered acyltransferase variants from Mycobacterium smegmatis (MsAcT) as the biocatalysts and vinyl acetate as irreversible acyl donor, yielding enantiomerically enriched (S)-alcohols and the corresponding (R)-acetates with E-values up to 328 and excellent optical purities (>99% ee). In general, higher ee-values were observed in the reactions catalyzed by lipases; however, the rates of the reactions were significantly better in the case of MsAcT-catalyzed enantioselective transesterifications. Interestingly, we have experimentally proved that enantiomerically enriched 1-(7-nitro-3,4-dihydroquinolin-1(2H)-yl)propan-2-ol undergoes spontaneous amplification of optical purity under achiral chromatographic conditions. Full article

Condensation of the reaction between enrofloxacin and ethylenediamine in the existence of glacial acetic acid produced a new N,N-ethylene (bis 1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6-fluoro-1,4-dihydroquinoline-3-carboxylic acid Schiff base (H₂Erx-en). H₂Erx-en was used as a tetra-dentate ligand to produce novel complexes by interacting with metal ions iron(III), yttrium(III), zirconium(IV), and lanthanum(III). The synthetic H₂Erx-en and its chelates had been detected with elemental analysis, spectroscopic methods, mass spectrometry, thermal studies, conductometric and magnetic measurements experiments. The calculated molar conductance of the complexes in 1 × 10⁻³ M DMF solution shows that iron(III), yttrium(III) and lanthanum(III) are 1:1 electrolytes, however the zirconium(IV) complex is non-electrolyte. The infrared spectra of H₂Erx-en chelates indicated that the carboxylic group is deprotonated and H₂Erx-en is associated with metals as a tetra-dentate through nitrogen and oxygen atoms. The disappearance of the carboxylic proton in all complexes corroborated information concerning H₂Erx-en deprotonation and complexation with metal ions, according to ¹H NMR data. Thermal analysis revealed the abundance of H₂O particles in the chelates’ entrance and outlet spheres, indicating the disintegration pattern of H₂Erx-en and their chelates. The Coats–Redfern and Horowitz–Metzeger approaches were utilized to calculate the thermodynamic items (E_a, ΔS *, ΔH *, and ΔG *) at n = 1 and n ≠ 1. The resulting data reveal better organized chelate building activation. Density functional theory (DFT) was created to properly grasp the optimal architecture of the molecules. The chelates are softer than H₂Erx-en, with estimates varying between 95.23 eV to 400.00 eV, compared to 31.47 eV for H₂Erx-en. The disc diffusion technique was utilized to assess H₂Erx-en and their chelates in an antimicrobial assay against various food and phytopathogens. The zirconium(IV) chelate has the most potent antibacterial action and is particularly efficient against Salmonella typhi. Full article

A N-(2,4-diaryltetrahydroquinolin-1-yl) furan-2-carboxamide derivative, [4-(3,4-dimethoxyphenyl)-3,6-dimethyl-2-phenyl-3,4-dihydroquinolin-1(2H)-yl)](furan-2-yl)methanone, was synthesized in a two-step procedure from p-toluidine, benzaldehyde, and trans-methyl-isoeugenol as commercial starting reagents through a sequence of Povarov cycloaddition reaction/N-furoylation processes. The structure of the compound was fully characterized by IR, ¹H, ¹³C-NMR, and X-ray diffraction data. Such types of derivatives are known as relevant therapeutic agents exhibiting potent anticancer, antibacterial, antifungal, anti-inflammatory, and immunological modulator properties. Full article

Quinolinones have been known for a long time as broad-spectrum synthetic antibiotics. More recently, the anticancer potential of this group of compounds has been investigated. Following this direction, we obtained a small library of 3-methylidene-1-sulfonyl-2,3-dihydroquinolin-4(1H)-ones with various substituents at positions 1, 2, 6, and 7 of the quinolinone ring system. The cytotoxic activity of the synthesized analogs was tested in the MTT assay on two cancer cell lines in order to determine the structure–activity relationship. All compounds produced high cytotoxic effects in MCF-7, and even higher in HL-60 cells. 2-Ethyl-3-methylidene-1-phenylsulfonyl-2,3-dihydroquinolin-4(1H)-one, which was over 5-fold more cytotoxic for HL-60 than for normal HUVEC cells, was selected for further tests. This analog was shown to inhibit proliferation and induce DNA damage and apoptosis in HL-60 cells. Full article

An organocatalytic [4 + 2] cascade annulation of salicylaldehydes and 1,3-bisarylsulfonylpropenes has been developed. This protocol enables the efficient and straightforward synthesis of a new series of 3-sulfonyl-2-sulfonylmethyl-2H-chromenes that are useful for exploring pharmacologically valued compounds. Further reductive modifications result in 3-desulfonylated chromene or chromane derivatives. This protocol can be expanded to the synthesis of 3-sulfonyl-2-sulfonylmethyl 1,2-dihydroquinoline. Full article

Herein we report the obtaining of 1-(3,4-dihydroquinolin-1(2H)-yl)-2- (4-isobutylphenyl)propan-1-one and its characterization. The newly obtained hybrid and its derivatives (hybrids of ibuprofen with 1,2,3,4-tetrahydroisoquinoline, and piperidine) were screened for their in vitro antioxidant, antitryptic, and inhibition of albumin denaturation activity. The lipophilicity was established using both reversed-phase thin layer chromatography and in silico calculations. Full article

In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D₂ (D₂R) modulators were synthesized and evaluated in vitro. The preliminary structure–activity relationship disclosed that compound 5e exhibited the highest D₂R affinity among the newly synthesized compounds. In addition, 5e showed a very low cytotoxic profile and a high probability to cross the blood–brain barrier, which is important considering the observed affinity. However, molecular modelling simulation revealed completely different binding mode of 5e compared to USC-D301, which might be the culprit of the reduced affinity of 5e toward D₂R in comparison with USC-D301. Full article