Bibliographic Details
| Title: |
Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides |
| Authors: |
Jiri Kos, Gilles Degotte, Dominika Pindjakova, Tomas Strharsky, Timotej Jankech, Tomas Gonec, Pierre Francotte, Michel Frederich, Josef Jampilek |
| Source: |
Molecules, Vol 27, Iss 22, p 7799 (2022) |
| Publisher Information: |
MDPI AG, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Organic chemistry |
| Subject Terms: |
cinnamanilides, antiplasmodial activity, Plasmodium, structure-activity relationships, Organic chemistry, QD241-441 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1420-3049 |
| Relation: |
https://www.mdpi.com/1420-3049/27/22/7799; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules27227799 |
| Access URL: |
https://doaj.org/article/168f27855ded41ada34cba2b3a7867c2 |
| Accession Number: |
edsdoj.168f27855ded41ada34cba2b3a7867c2 |
| Database: |
Directory of Open Access Journals |
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