[en] 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 addi- tion, (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-BlueTM 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Kos, Jiri
Degotte, Gilles ; Université de Liège - ULiège > Université de Liège - ULiège
Pindjakova, Dominika
Strharsky, Tomas
Jankech, Timotej
Gonec, Tomas
Francotte, Pierre ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Frederich, Michel ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Jampilek, Josef
Language :
English
Title :
Insights into Antimalarial Activity of N-Phenyl- Substituted Cinnamanilides
Publication date :
2022
Journal title :
Molecules
eISSN :
1420-3049
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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