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Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides.
| Content Provider | Europe PMC |
|---|---|
| Author | Kos, Jiri Degotte, Gilles Pindjakova, Dominika Strharsky, Tomas Jankech, Timotej Gonec, Tomas Francotte, Pierre Frederich, Michel Jampilek, Josef |
| Editor | Elhabiri, Mourad Song, Baoan |
| Copyright Year | 2022 |
| Abstract | 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 IC50 from 0.58 to 31 µM, whereas (2E)-N-(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide (24) was the most effective agent (IC50 = 0.58 µM). In addition, (2E)-N-[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide (36), (2E)-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide (18), (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide (23), and (2E)-3-phenyl-N-(3,4,5-trichlorophenyl)prop-2-enamide (33) demonstrated efficacy in the IC50 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. |
| Journal | Molecules |
| Volume Number | 27 |
| DOI | 10.3390/molecules27227799 |
| PubMed Central reference number | PMC9698057 |
| Issue Number | 22 |
| PubMed reference number | 36431900 |
| e-ISSN | 14203049 |
| Language | English |
| Publisher | Molecular Diversity Preservation International (MDPI) |
| Publisher Date | 2022-11-12 |
| Access Restriction | Open |
| Subject Keyword | cinnamanilides antiplasmodial activity Plasmodium structure-activity relationships |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physical and Theoretical Chemistry Medicine Chemistry Drug Discovery Pharmaceutical Science Analytical Chemistry Molecular Medicine Organic Chemistry |
