69063-03-2Relevant articles and documents
Synthesis, docking and in vitro antimalarial evaluation of bifunctional hybrids derived from β-lactams and 7-chloroquinoline using click chemistry
Singh, Pardeep,Singh, Parvesh,Kumar, Malkeet,Gut, Jiri,Rosenthal, Philip J.,Kumar, Kewal,Kumar, Vipan,Mahajan, Mohinder P.,Bisetty, Krishna
, p. 57 - 61 (2012)
1,2,3-Triazole tethered β-lactam and 7-chloroquinoline bifunctional hybrids were synthesized and evaluated as potential antimalarial agents. Activity against cultured Plasmodium falciparum was dependent on the N-substituent of the β-lactam ring as well as
Pyrimidine-chloroquinoline hybrids: Synthesis and antiplasmodial activity
Chopra, Rakesh,Chibale, Kelly,Singh, Kamaljit
, p. 39 - 53 (2018)
Triazole tethered 7-chloroquinoline-pyrimidine-5-carboxylate hybrids were synthesized and evaluated for antiplasmodial activity against chloroquine sensitive (CQS) NF54 strain of Plasmodium falciparum. The most active hybrids of the series were
A simple quinoline salt derivative is active in vitro against Plasmodiumf alciparum asexual blood stages and inhibits the development of cerebral malaria in murine model
Azevedo, Marina Rocha,Barreto, Livia Maria,Bezerra Bellei, Jessica Correa,Coimbra, Elaine Soares,David da Silva, Adilson,Gualberto Pereira, Henrique Marcelo,Karine da Costa Nunes, Isabelle,Marques, Carolina Brandi,Renhe, Daniela Chaves,Rocha, Vinicius Novaes,de Pilla Varotti, Fernando,Carpinter, Bárbara Albuquerque,Ferraz Coelho, Eduardo Ant?nio,Glanzmann, Nícolas,Gorza Scopel, Kézia Katiani
, (2022/02/17)
Chloroquine (CQ) was the most effective and widely used drug for the prophylaxis and treatment of severe and non-severe malaria. Although its prophylactic use has led to resistance to P. falciparum in all endemic countries, CQ still remains the drug of choice for the treatment of vivax malaria. Otherwise, the speed in which parasite resistance to available antimalarials rises and spreads in endemic regions points to the urgent need for the development of new antimalarials. Quinoline derivatives have been used as a tool in the search for new drugs and were investigated in the present study in an attempt to produce a HIT compound to avoid the cerebral malarial (CM). Seven compounds were synthesized, including three quinoline derivate salts. The cytotoxicity and antiplasmodial activity were assayed in vitro, highlighting compound 3 as a HIT, which also showed interaction with ferriprotoporphyrin IX similarly to CQ. Physicochemical and pharmacokinetic properties of absorption were found to be favorable when analyzed in silico. The in vivo assays, using the experimental cerebral malaria (ECM) model, showed important values of parasite growth inhibition on the 7th day-post infection (Q15 15 mg/kg: 76.9%, Q30 30 mg/kg: 90,1% and Q50 50 mg/kg: 92,9%). Compound 3 also showed significant protection against the development of CM, besides hepatic and renal parameters better than CQ. In conclusion, this quinoline derivative demonstrated promising activity for the treatment of malaria and was able to avoid the development of severe malaria in mice.
Synthesis and biological activity profile of novel triazole/quinoline hybrids
Azerang, Parisa,Jamshidi, Hoda,Naimi-Jamal, Mohammad Reza,RayatSanati, Kimia,Safavi, Maliheh,Tahghighi, Azar
, (2022/02/23)
Based on the significant and diverse pharmacophore features of triazole ring and considering the potent antimicrobial properties of quinoline scaffold, a novel series of 1,2,3-triazole-based polyaromatic compounds containing chloroquinoline moiety were synthesized through a well-established synthetic methodology, named click chemistry. The structure of the synthetic compounds was characterized by various spectroscopic methods. The final products of triazole/quinoline hybrids and ((prop-2-yn-1-yloxy)methyl)benzene intermediates were screened for their antibacterial (Staphylococcus aureus, Escherichia coli, Shigella flexneri, and Salmonella enterica), antifungal (Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus), and cytotoxic activities. The best antifungal compounds exhibited minimum inhibitory concentration (MIC), in the range of 0.35–0.63?μM, against S.?cerevisiae without any cytotoxic effect. These compounds can be selected as the potential candidates for treating invasive fungal infections caused by S.?cerevisiae, after further investigation. Preliminary in silico ADME studies also predicted the favorable pharmacokinetic attributes of most compounds.
Rational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors
Adigun, Rasheed A.,Balogun, Mohammed O.,Malan, Frederick P.,October, Natasha
, (2022/03/27)
A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesised based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a methyl group to bring the molecular weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesised compounds in addition to the previously identified hits were subjected to molecular docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimised to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimised ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesised compounds indicate that these compounds possess good pharmacokinetic properties.
Anti-skin tumor compound and application thereof
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Paragraph 0084-0086, (2021/07/28)
The invention relates to an anti-skin tumor compound and application thereof. The anti-skin tumor compound has a structure represented by the following structural formula I. The anti-skin tumor compound disclosed by the invention can effectively inhibit proliferation of skin tumor cells, and especially has the minimum semi-inhibitory concentrations of 130nM and 80nM for human skin malignant melanoma cells SK-Mel-5 and SK-Mel-28 respectively, so that the anti-skin tumor compound is proved to have extremely strong capability of inducing apoptosis of the skin tumor cells, and can be applied to preparation of anti-skin tumor drugs.
Unravelling the potency of triazole analogues for inhibiting α-synuclein fibrillogenesis andin vitrodisaggregation
Maqbool, Mudasir,Gadhavi, Joshna,Singh, Anju,Hivare, Pravin,Gupta, Sharad,Hoda, Nasimul
supporting information, p. 1589 - 1603 (2021/03/01)
A series of triazole-based compounds was synthesized using a click chemistry approach and evaluated for the inhibition of α-synuclein (α-syn) fibrillogenesis and its disaggregation. CompoundsTr3,Tr7,Tr12,Tr15, andTr16exhibited good effect in inhibiting α-
Synthesis and antiplasmodial evaluation of 1H-1,2,3-triazole grafted 4-aminoquinoline-benzoxaborole hybrids and benzoxaborole analogues
Saini, Anu,Kumar, Sumit,Raj, Raghu,Chowdhary, Shefali,Gendrot, Mathieu,Mosnier, Joel,Fonta, Isabelle,Pradines, Bruno,Kumar, Vipan
, (2021/02/26)
A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-
Quinoline-triazole half-sandwich iridium(iii) complexes: Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies
Barnett, Christopher B.,Melis, Diana R.,Nordlander, Ebbe,Smith, Gregory S.,Wiesner, Lubbe
, p. 11543 - 11555 (2020/09/07)
Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the Plasmodium falciparum malaria parasite. Supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. Single crystal X-ray diffraction confirmed the proposed molecular structures of both isolated kinetic and thermodynamic products. Complexation with iridium significantly enhances the in vitro activity of selected ligands against the chloroquine-sensitive (NF54) Plasmodium falciparum strain, with selected complexes being over one hundred times more active than their respective ligands. No cross-resistance was observed in the chloroquine-resistant (K1) strain. No cytotoxicity was observed for selected complexes tested against the mammalian Chinese Hamster Ovarian (CHO) cell line. In addition, speed-of-action assays and β-haematin inhibition studies were performed. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes can act as transfer hydrogenation catalysts, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of a hydrogen source, sodium formate.
Synthesis, Biological Evaluation and in Silico Computational Studies of 7-Chloro-4-(1 H-1,2,3-triazol-1-yl)quinoline Derivatives: Search for New Controlling Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae) Larvae
Rosado-Solano, Doris Natalia,Barón-Rodríguez, Mario Alberto,Sanabria Florez, Pedro Luis,Luna-Parada, Luz Karime,Puerto-Galvis, Carlos Eduardo,Zorro-González, Andrés Felipe,Kouznetsov, Vladimir V.,Vargas-Méndez, Leonor Yamile
, p. 9210 - 9219 (2019/09/03)
The insecticidal and antifeedant activities of five 7-chloro-4-(1H-1,2,3-triazol-1-yl)quinoline derivatives were evaluated against the maize armyworm, Spodoptera frugiperda (J.E. Smith). These hybrids were prepared through a copper-catalyzed azide alkyne
