| Autor: |
Kos J; Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.; Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia., Degotte G; I2BM, Department of Molecular Chemistry, University Grenoble-Alpes, Rue de la Chimie 570, 38610 Gieres, France., Pindjakova D; Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia., Strharsky T; Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho 1946/1, 61200 Brno, Czech Republic., Jankech T; Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia., Gonec T; Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho 1946/1, 61200 Brno, Czech Republic., Francotte P; Laboratory of Medicinal Chemistry, CIRM, Department of Pharmacy, University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium., Frederich M; Laboratory of Pharmacognosy, CIRM, Department of Pharmacy, University of Liege, Avenue Hippocrate 15, 4000 Liege, Belgium., Jampilek J; Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia.; Department of Chemical Biology, Faculty of Science, Palacky University Olomouc, Slechtitelu 27, 78371 Olomouc, Czech Republic. |
| Abstrakt: |
Due to the urgent need of innovation in the antimalarial therapeutic arsenal, a series of thirty-seven ring-substituted N -arylcinnamanilides prepared by microwave-assisted synthesis were subjected to primary screening against the chloroquine-sensitive strain of P. falciparum 3D7/MRA-102. The lipophilicity of all compounds was experimentally determined as the logarithm of the capacity factor k , and these data were subsequently used in the discussion of structure-activity relationships. Among the screened compounds, fourteen derivatives exhibited IC 50 from 0.58 to 31 µM, whereas (2 E )- N -(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide ( 24 ) was the most effective agent (IC 50 = 0.58 µM). In addition, (2 E )- N -[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide ( 36 ), (2 E )- N -[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide ( 18 ), (2 E )- N -(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide ( 23 ), and (2 E )-3-phenyl- N -(3,4,5-trichlorophenyl)prop-2-enamide ( 33 ) demonstrated efficacy in the IC 50 range from 2.0 to 4.3 µM, comparable to the clinically used standard chloroquine. The results of a cell viability screening performed using THP1-Blue™ NF-κB cells showed that none of these highly active compounds displayed any significant cytotoxic effect up to 20 μM, which makes them promising Plasmodium selective substances for further investigations. |
