An electrochemical reaction between quinoline N-oxides and morpholine was developed by using Cu(OAc)sub.2 as a catalyst, generating products of 4-aminoquinoline N-oxides in CHsub.2Clsub.2 or ...2-aminoquinoline N-oxides in CHsub.3CN in good yields. With an increase in the amount of electricity passed, the product deoxygenates with the formation of aminoquinolines. The advantages of the reaction are mild conditions, room temperature, the use of morpholine rather than its derivatives, and the ability to control the process when the electrolysis conditions change. Bisubstituted quinoline has also been obtained. The redox properties of both individual participants of C–H/N–H cross-coupling and multicomponent systems were established by voltammetry and EPR methods. For the first time, the EPR spectrum of the morpholine radical was recorded at room temperature, and its magnetic resonance parameters were determined in CHsub.2Clsub.2. Mechanisms for the catalytic reaction have been proposed. This is a simple and easy-to-perform method for introducing a morpholine substituent, important in medicinal chemistry and other fields, by C–H/N–H cross-coupling.
A novel method for synthesizing 1,2,4-triazole- and tetrazole-containing 4H-thiopyrano2,3-bquinolines using a new combination of the thio-Michael and aza-Morita–Baylis–Hillman reactions was ...developed. Target compounds were evaluated for their cytotoxicities and antiviral activities against influenza A/Puerto Rico/8/34 virus in MDCK cells. The compounds showed low toxicity and some exhibited moderate antiviral activity. Molecular docking identified the M2 channel and polymerase basic protein 2 as potential targets. We observed that the antiviral activity of thiopyrano2,3-bquinolines is notably affected by both the nature and position of the substituent within the tetrazole ring, as well as the substituent within the benzene moiety of quinoline. These findings contribute to the further search for new antiviral agents against influenza A viruses among derivatives of thiopyrano2,3-bquinoline.
Several quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT interval prolongation. A prolonged ...QT interval is a sensitive but not specific risk marker for the development of Torsade de Pointes-a potentially lethal polymorphic ventricular tachyarrhythmia. The increasing use of quinoline and structurally related antimalarials in mass treatments to eliminate malaria rapidly highlights the need to review their cardiovascular safety profiles.
The primary objective of this systematic review was to describe the documented clinical and electrocardiographic cardiovascular side effects of quinine, mefloquine, lumefantrine, piperaquine, halofantrine, chloroquine, sulfadoxine-pyrimethamine, amodiaquine, and primaquine. Trials in healthy subjects or patients with Plasmodium falciparum or P. vivax infection were included if at least two ECGs were conducted during the trial. All trial designs were included except case reports and pooled analyses. Secondary outcomes were the methods adopted by trials for measuring and reporting the QT interval.
Data from trials published between 1982 and July 2016 were included. A total of 177 trials met the inclusion criteria. 35,448 participants received quinoline antimalarials in these trials, of which 18,436 participants underwent ECG evaluation. Subjects with co-medication use or comorbidities including cardiovascular disease were excluded from the majority of trials. Dihydroartemisinin-piperaquine was the drug most studied (5083 participants). Despite enormous use over the past 60 years, only 1076, 452, and 150 patients had ECG recordings reported in studies of chloroquine, amodiaquine, and primaquine respectively. Transiently high concentrations of quinine, quinidine, and chloroquine following parenteral administration have all been associated with hypotension, but there were no documented reports of death or syncope attributable to a cardiovascular cause, nor of electrocardiographic recordings of ventricular arrhythmia in these trials. The large volume of missing outcome information and the heterogeneity of ECG interval reporting and measurement methodology did not allow pooled quantitative analysis of QT interval changes.
No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation. While these findings provide further evidence of the rarity of serious cardiovascular events after treatment with these drugs, they also underscore the need for continued strengthening of pharmacovigilance systems for robust detection of rare drug adverse events in real-world populations. A standardised approach to measurement and reporting of ECG data in malaria trials is also needed.
PROSPERO CRD42016036678.
Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine, amodiaquine, mefloquine and ...sulfadoxine, were used as inspiration. We demonstrated the importance of quinoline and non-quinoline derivatives in vitro with activity against the W2 chloroquine-resistant (CQR)
clone strain and in vivo against
-infected mouse model. Among the quinoline derivatives, new hybrids between chloroquine and sulfadoxine were designed, which gave rise to an important prototype that was more active than both chloroquine and sulfadoxine. Hybrids between chloroquine-atorvastatin and primaquine-atorvastatin were also synthesized and shown to be more potent than the parent drugs alone. Additionally, among the quinoline derivatives, new mefloquine derivatives were synthesized. Among the non-quinoline derivatives, we obtained excellent results with the triazolopyrimidine nucleus, which gave us prototype
that inspired the synthesis of new heterocycles. The pyrazolopyrimidine derivatives stood out as non-quinoline derivatives that are potent inhibitors of the
dihydroorotate dehydrogenase (
DHODH) enzyme. We also examined the pyrazolopyridine and pyrazolopyrimidine nuclei.
Among heterocyclic compounds, quinoline scaffold has become an important construction motif for the development of new drugs. Quinoline and its derivatives possess many types of biological activities ...and have been reported to show significant anticancer activity. Quinoline compounds play an important role in anticancer drug development as they have shown excellent results through different mechanism of action such as growth inhibitors by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration and modulation. A number of quinoline derivatives have been reported till date for their anticancer activity. The present review, summarizes various mono-, di-, tri-, tetra- and heterocyclic substituent quinoline derivatives with potential anticancer activity. Their mechanism of action and possible structure activity relationship has also been discussed.
The design of prodrugs is one of the important strategies for selective anti-cancer therapies. When designing prodrugs, attention is paid to the possibility of their targeting tumor-specific markers ...such as proteins responsible for glucose uptake. That is why glycoconjugation of biologically active compounds is a frequently used strategy. Glycoconjugates consisting of three basic building blocks: a sugar unit, a linker containing a 1,2,3-triazole ring, and an 8-hydroxyquinoline fragment was described earlier. It is not known whether their cytotoxicity is due to whole glycoconjugates action or their metabolites. To check the biological activity of products that can be released from glycoconjugates under the action of hydrolytic enzymes, the synthetically obtained potential metabolites were tested in vitro for the inhibition of proliferation of HCT-116, MCF-7, and NHDF-Neo cell lines using the MTT assay. Research shows that for the full activity of glycoconjugates, the presence of all three building blocks in the structure of a potential drug is necessary. For selected derivatives, additional tests of targeted drug delivery to tumor cells were carried out using polymer nanocarriers in which they are encapsulated. This approach significantly lowered the determined IC
values of the tested compounds and improved their selectivity and effectiveness.
The X-ray structure analyses of 4-hydroxy-1-methylquinolin-2(1H)-one (1), 6-ethyl-4-hydroxy-2H-pyrano3,2-cquinoline-2,5(6 H)-dione (2), (E)-4-(2-benzylidene-hydrazineyl)quinolin-2(1H)-one (3), and ...diethyl (E)-2-(2-(1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)hydrazineylidene)-succinate (4), were carried out. The aforementioned compounds showed strong intramolecular hydrogen bonds which play important roles in the crystal packing of them. Graphical
Simple synthetic methods are described for the synthesis of valuable polyfunctional brominated methoxyquinolines 10–13, 20–21, and 24–25. Three regioselective routes are described for convenient ...preparation of brominated methoxyquinolines at the C-2, C-3, and C-5 positions with consecutive reaction steps under mild reaction conditions using molecular bromine. While bromination of 6-bromo-8-methoxy-1,2,3,4-tetrahydroquinoline (8) selectively gave 3,6-dibromo-8-methoxyquinoline (10) and 3,5,6-tribromo-8-methoxyquinoline (11), the reaction of 6,8-dimethoxy-1,2,3,4-tetrahydroquinoline (9) resulted in the formation of 3-bromo-6,8-dimethoxyqinoline (12) and tribromide 13. On the other hand, direct bromination of 6-methoxy- 17 and 6,8-dimethoxyquinoline (19) gave 5-bromo derivatives 20 and 21. However, the reaction 3,6-dimethoxyquinoline (8) resulted in dibromination to form 2,5-dibromoquinoline (24). This process selectively led to functionalization of the quinoline ring at both the C-2 and C-5 positions.
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A series of 5-alkoxy-1,2,4triazolo4,3-
aquinoline derivatives were synthesized using 4-hydroxyquinolin-2(1
H)-one as the starting material. Their anticonvulsant activities were evaluated by the ...maximal electroshock test (MES) and their neurotoxicities were measured by the rotarod test. The results of these tests demonstrated that 5-hexyloxy-1,2,4triazolo4,3-
aquinoline (
3f) was the most potent anticonvulsant, with median effective dose (ED
50) of 19.0
mg/kg and protective index (PI
=
TD
50/ED
50) values of 5.8 in the MES test. Compound 5-benzyloxy-1,2,4triazolo4,3-
aquinoline (
3j), exhibited a little weaker activity than compound
3f in controlling the seizure induced by MES test at the dose of 22.8
mg/kg, but it possessed lower neurotoxicity with PI value of 12.0, which was safer than marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, compound
3j was tested in pentylenetetrazole test, isoniazid test, thiosemicarbazide test, 3-mercaptopropionic acid and strychnine test.
Display omitted A new series of 5-alkoxy-1,2,4triazolo4,3-
aquinoline derivatives are herein reported. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test.
In vivo fluorescent monitoring of physiological processes with high‐fidelity is essential in disease diagnosis and biological research, but faces extreme challenges due to aggregation‐caused ...quenching (ACQ) and short‐wavelength fluorescence. The development of high‐performance and long‐wavelength aggregation‐induced emission (AIE) fluorophores is in high demand for precise optical bioimaging. The chromophore quinoline‐malononitrile (QM) has recently emerged as a new class of AIE building block that possesses several notable features, such as red to near‐infrared (NIR) emission, high brightness, marked photostability, and good biocompatibility. In this minireview, we summarize some recent advances of our established AIE building block of QM, focusing on the AIE mechanism, regulation of emission wavelength and morphology, the facile scale‐up and fast preparation for AIE nanoparticles, as well as potential biomedical imaging applications.
In this Minireview, recent advances related to the aggregation‐induced emission (AIE) building block quinoline‐malononitrile are summarized. It focuses on the AIE mechanism, regulation of emission wavelength and morphology, the facile scale‐up and fast preparation for AIE nanoparticles, and potential biomedical imaging applications.
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