53977-28-9Relevant academic research and scientific papers
ICI 56,780 optimization: Structure-activity relationship studies of 7-(2-phenoxyethoxy)-4(1H)-quinolones with antimalarial activity
Maignan, Jordany R.,Lichorowic, Cynthia L.,Giarrusso, James,Blake, Lynn D.,Casandra, Debora,Mutka, Tina S.,LaCrue, Alexis N.,Burrows, Jeremy N.,Willis, Paul A.,Kyle, Dennis E.,Manetsch, Roman
, p. 6943 - 6960 (2016/08/05)
Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.
Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2
Golub, Andriy G.,Yakovenko, Olexander Ya.,Bdzhola, Volodymyr G.,Sapelkin, Vladislav M.,Zien, Piotr,Yarmoluk, Sergiy M.
, p. 6443 - 6450 (2007/10/03)
Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitors-3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC 50 = 0.3 μM) and 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (9) (IC50 = 1 μM), are ATP competitive (Ki values are 0.06 and 0.28 μM, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.
