1361005-11-9Relevant academic research and scientific papers
2-Arylquinolines as novel anticancer agents with dual EGFR/FAK kinase inhibitory activity: synthesis, biological evaluation, and molecular modelling insights
Elbadawi, Mostafa M.,Eldehna, Wagdy M.,Abd El-Hafeez, Amer Ali,Somaa, Warda R.,Albohy, Amgad,Al-Rashood, Sara T.,Agama, Keli K.,Elkaeed, Eslam B.,Ghosh, Pradipta,Pommier, Yves,Abe, Manabu
, p. 349 - 372 (2021/12/24)
In this study, different assortments of 2-arylquinolines and 2,6-diarylquinolines have been developed. Recently, we have developed a new series of 6,7-dimethoxy-4-alkoxy-2-arylquinolines as Topoisomerase I (TOP1) inhibitors with potent anticancer activity. Utilising the SAR outputs from this study, we tried to enhance anticancer and TOP1 inhibitory activities. Though target quinolines demonstrated potent antiproliferative effect, specifically against colorectal cancer DLD-1 and HCT-116, they showed weak TOP1 inhibition which may be attributable to their non-coplanarity. Thereafter, screening against kinase panel revealed their dual inhibitory activity against EGFR and FAK. Quinolines 6f, 6h, 6i, and 20f were the most potent EGFR inhibitors (IC50s = 25.39, 20.15, 22.36, and 24.81 nM, respectively). Meanwhile, quinolines 6f, 6h, 6i, 16d, and 20f exerted the best FAK inhibition (IC50s = 22.68, 14.25, 18.36, 17.36, and 15.36 nM, respectively). Finally, molecular modelling was employed to justify the promising EGFR/FAK inhibition. The study outcomes afforded the first reported quinolines with potent EGFR/FAK dual inhibition.
4-aminoquinoline compound, and preparation method and application thereof
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Paragraph 0032; 0039-0042, (2019/11/12)
The invention discloses a 4-aminoquinoline compound, and a preparation method and application thereof. The second site of the 4-aminoquinoline compound is replaced by cyclic R-base, the 4-aminoquinoline compound is obtained by 4-step reaction of anthranil
Direct synthesis of 2-aryl-4-quinolones via transition-metal-free intramolecular oxidative C(sp3)-H/C(sp3)-H coupling
Hu, Wei,Lin, Jian-Ping,Song, Li-Rui,Long, Ya-Qiu
supporting information, p. 1268 - 1271 (2015/05/20)
A novel, metal-free oxidative intramolecular Mannich reaction was developed between secondary amines and unmodified ketones, affording a simple and direct access to a broad range of 2-arylquinolin-4(1H)-ones through C(sp3)-H activation/C(sp3)-C(sp3) bond formation from readily available N-arylmethyl-2-aminophenylketones, using TEMPO as the oxidant and KOtBu as the base.
Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:Quinone oxidoreductase (PfNDH2)
Pidathala, Chandrakala,Amewu, Richard,Pacorel, Bénédicte,Nixon, Gemma L.,Gibbons, Peter,Hong, W. David,Leung, Suet C.,Berry, Neil G.,Sharma, Raman,Stocks, Paul A.,Srivastava, Abhishek,Shone, Alison E.,Charoensutthivarakul, Sitthivut,Taylor, Lee,Berger, Olivier,Mbekeani, Alison,Hill, Alasdair,Fisher, Nicholas E.,Warman, Ashley J.,Biagini, Giancarlo A.,Ward, Stephen A.,O'Neill, Paul M.
, p. 1831 - 1843 (2012/05/04)
A program was undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with a range of chemoinformatics methods in the rational selection of 17 000 compounds for high-throughput screening. Twelve distinct chemotypes were identified and briefly examined leading to the selection of the quinolone core as the key target for structure-activity relationship (SAR) development. Extensive structural exploration led to the selection of 2-bisaryl 3-methyl quinolones as a series for further biological evaluation. The lead compound within this series 7-chloro-3-methyl-2-(4-(4-(trifluoromethoxy)benzyl)phenyl) quinolin-4(1H)-one (CK-2-68) has antimalarial activity against the 3D7 strain of P. falciparum of 36 nM, is selective for PfNDH2 over other respiratory enzymes (inhibitory IC50 against PfNDH2 of 16 nM), and demonstrates low cytotoxicity and high metabolic stability in the presence of human liver microsomes. This lead compound and its phosphate pro-drug have potent in vivo antimalarial activity after oral administration, consistent with the target product profile of a drug for the treatment of uncomplicated malaria. Other quinolones presented (e.g., 6d, 6f, 14e) have the capacity to inhibit both PfNDH2 and P. falciparum cytochrome bc1, and studies to determine the potential advantage of this dual-targeting effect are in progress.
