837-52-5Relevant articles and documents
Design and synthesis of 4-piperazinyl quinoline derived urea/thioureas for anti-breast cancer activity by a hybrid pharmacophore approach
Viswas, Raja Solomon,Pundir, Sheetal,Lee, Hoyun
, p. 620 - 630 (2019)
In an attempt to improve anti-breast cancer activity, a new series of 4-piperazinylquinoline derivatives based on the urea/thiourea scaffold were designed and synthesised by a pharmacophore hybrid approach. We then examined for their antiproliferative eff
Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives
Chiyanzu, Idan,Clarkson, Cailean,Smith, Peter J.,Lehman, Julie,Gut, Jiri,Rosenthal, Philip J.,Chibale, Kelly
, p. 3249 - 3261 (2005)
A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum. These derivatives showed anti-plasmodial
Design and synthesis of quinoline-pyrimidine inspired hybrids as potential plasmodial inhibitors
Kayamba, Francis,Malimabe, Teboho,Ademola, Idowu Kehinde,Pooe, Ofentse Jacob,Kushwaha, Narva Deshwar,Mahlalela, Mavela,van Zyl, Robyn L.,Gordon, Michelle,Mudau, Pertunia T.,Zininga, Tawanda,Shonhai, Addmore,Nyamori, Vincent O.,Karpoormath, Rajshekhar
, (2021/03/22)
Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed. In line with this
Quinoline carboxamide core moiety-based compounds inhibit P. falciparum falcipain-2: Design, synthesis and antimalarial efficacy studies
Singh, Anju,Kalamuddin, Md,Maqbool, Mudasir,Mohmmed, Asif,Malhotra, Pawan,Hoda, Nasimul
supporting information, (2020/12/07)
Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC50 4.78, 7.37, 2.14 and 2.64 μM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.
Design, synthesis and study of antibacterial and antitubercular activity of quinoline hydrazone hybrids
Eswaran, Sumesh,Shruthi, T. G.,Subramanian, Sangeetha
, p. 137 - 147 (2020/11/12)
Emerging bacterial resistance is causing widespread problems for the treatment of various infections. Therefore, the search for antimicrobials is a never-ending task. Hydrazones and quinolines possess a wide variety of biological activities. Herewith, eleven quinoline hydrazone derivatives have been designed, synthesized, characterized and evaluated for their antibacterial activity and antitubercular potential against Mtb WT H37Rv. Compounds QH-02, QH-04 and QH-05 were found to be promising compounds with an MIC value of 4 μg/mL against Mtb WT H37Rv. Compounds QH-02, QH-04, QH-05, and QH-11 were also found to be active against bacterial strains including Acinetobacter baumanii, Escherichia coli and Staphylococcus aureus. Further, we have carried out experiments to confirm the cytotoxicity of the active compounds and found them to be non-toxic.
Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery
Solbak, Sara Marie ?ie,Zang, Jie,Narayanan, Dilip,H?j, Lars Jakobsen,Bucciarelli, Saskia,Softley, Charlotte,Meier, Sebastian,Langkilde, Annette Eva,Gotfredsen, Charlotte Held,Sattler, Michael,Bach, Anders
, p. 1156 - 1177 (2020/03/10)
Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phoxSH3A-B) with KD values of 400-600 μM. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phoxSH3A-B and these competed with p22phox for binding to p47phoxSH3A-B. Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phoxSH3A-B-p22phox interaction (Ki of 20 μM). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.
Synthesis of Novel G Factor or Chloroquine-Artemisinin Hybrids and Conjugates with Potent Antiplasmodial Activity
Athanassopoulos, Constantinos M.,Baltas, Michel,Grellier, Philippe,Menendez, Christophe,Mouray, Elisabeth,Papaioannou, Dionissios,Pepe, Dionissia A.,Toumpa, Dimitra,André-Barrès, Christiane
supporting information, p. 921 - 927 (2020/07/21)
A series of novel hybrids of artemisinin (ART) with either a phytormone endoperoxide G factor analogue (GMeP) or chloroquine (CQ) and conjugates of the same compounds with the polyamines (PAs), spermidine (Spd), and homospermidine (Hsd) were synthesized and their antiplasmodial activity was evaluated using the CQ-resistant P. falciparum FcB1/Colombia strain. The ART-GMeP hybrid 5 and compounds 9 and 10 which are conjugates of Spd and Hsd with two molecules of ART and one molecule of GMeP, were the most potent with IC50 values of 2.6, 8.4, and 10.6 nM, respectively. The same compounds also presented the highest selectivity indexes against the primary human fibroblast cell line AB943 ranging from 16 372 for the hybrid 5 to 983 for the conjugate 10 of Hsd.
Method for synthesizing piperaquine intermediate in continuous flow microreactor
-
Paragraph 0026-0040, (2019/10/02)
The invention discloses a method for synthesizing a piperaquine intermediate by means of a microchannel reactor, and belongs to the technical field of synthesis of antimalarial medicines. The method comprises the steps of dissolving piperaquine in an appropriate amount of water as a material I, dissolving 4,7-dichloroquinoline in an organic solvent as a material, and transporting the material I toa preheating module of the microchannel reactor for preheating; and transporting the preheated material I to a reaction module set of the microchannel reactor, meanwhile, directly transporting the material into the reaction module set of the microchannel reactor, making the material I and the material subjected to condensation reaction, collecting reaction liquid which flows out of an outlet of the microchannel reactor, and obtaining 7-chloro-4-piperazinoquinoline after conducting post-treatment on the reaction liquid. By means of the synthesis method, reaction time can be effectively shortened, so that acid non-soluble substance impurities are greatly reduced.
Method for producing piperaquine phosphate intermediate quinoline piperazine hydrochloride through application of piperazine
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Paragraph 0045-0049, (2020/01/04)
The invention discloses a method for preparing high-purity quinoline piperazine hydrochloride, which has the advantages of simple process, easy purification of the product, no less than 99.5% of purity, avoidance of toxic reagents, small environmental pollution, low production cost and suitability for industrial production. The invention further discloses a method for producing quinoline piperazine hydrochloride through application of piperazine, wherein piperazine does not need to be separated from mother liquor, and the mother liquor is directly applied to production of quinoline piperazinehydrochloride of the next batch, the method is small in environmental pollution and low in production cost, the yield of the intermediate quinoline piperazine hydrochloride is increased, and the production cost is reduced.
Synthesis, antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1,2,4-oxadiazole moiety
Shruthi,Eswaran, Sumesh,Shivarudraiah, Prasad,Narayanan, Shridhar,Subramanian, Sangeetha
supporting information, p. 97 - 102 (2018/11/23)
Tuberculosis is the infectious disease caused by mycobacterium tuberculosis (Mtb), responsible for the utmost number of deaths annually across the world. Herein, twenty-one new substituted 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl-quinoline derivatives were designed and synthesized through multistep synthesis followed by in vitro evaluation of their antitubercular potential against Mtb WT H37Rv. The compound QD-18 was found to be promising with MIC value of 0.5 μg/ml and QD-19 to QD-21 were also remarkable with MIC value of 0.25 μg/ml. Additionally, we have carried out experiments to confirm the metabolic stability, cytotoxicity and pharmacokinetics of these compounds along with kill kinetics of QD-18. These compounds were found to be orally bioavailable and highly effective. Altogether, these results indicate that QD-18, QD-19, QD-20 and QD-21 are promising lead compounds for the development of a novel chemical class of antitubercular drugs.
