Insights into Antimalarial Activity of N-Phenyl-Substituted
Cinnamanilides

J 2022

Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides

KOS, Jiří; Gilles DEGOTTE; Dominika PINDJAKOVA; Tomáš STRHÁRSKY; Timotej JANKECH et al.

Basic information

Original name

Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides

Authors

KOS, Jiří; Gilles DEGOTTE; Dominika PINDJAKOVA; Tomáš STRHÁRSKY; Timotej JANKECH; Tomáš GONĚC; Pierre FRANCOTTE; Michel FREDERICH and Josef JAMPILEK

Edition

Molecules, Basel, MDPI, 2022, 1420-3049

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 4.600

Marked to be transferred to RIV

Yes

RIV identification code

RIV/00216224:14110/22:00127693

Organization unit

Faculty of Medicine

Keywords in English

cinnamanilides; antiplasmodial activity; Plasmodium; structure-activity relationships

Abstract

In the original language

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.

Cite

KOS, Jiří; Gilles DEGOTTE; Dominika PINDJAKOVA; Tomáš STRHÁRSKY; Timotej JANKECH; Tomáš GONĚC; Pierre FRANCOTTE; Michel FREDERICH and Josef JAMPILEK. Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides. Molecules. Basel: MDPI, 2022, vol. 27, No 22, p. 1-10. ISSN 1420-3049. Available from: https://doi.org/10.3390/molecules27227799.

@article{2243545,
   author = {Kos, Jiří and Degotte, Gilles and Pindjakova, Dominika and Strhársky, Tomáš and Jankech, Timotej and Goněc, Tomáš and Francotte, Pierre and Frederich, Michel and Jampilek, Josef},
   article_location = {Basel},
   article_number = {22},
   doi = {https://doi.org/10.3390/molecules27227799},
   keywords = {cinnamanilides; antiplasmodial activity; Plasmodium; structure-activity relationships},
   language = {eng},
   issn = {1420-3049},
   journal = {Molecules},
   title = {Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides},
   url = {https://www.mdpi.com/1420-3049/27/22/7799},
   volume = {27},
   year = {2022}
}

TY  - JOUR
ID  - 2243545
AU  - Kos, Jiří - Degotte, Gilles - Pindjakova, Dominika - Strhársky, Tomáš - Jankech, Timotej - Goněc, Tomáš - Francotte, Pierre - Frederich, Michel - Jampilek, Josef
PY  - 2022
TI  - Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides
JF  - Molecules
VL  - 27
IS  - 22
SP  - 1-10
EP  - 1-10
PB  - MDPI
SN  - 14203049
KW  - cinnamanilides
KW  - antiplasmodial activity
KW  - Plasmodium
KW  - structure-activity relationships
UR  - https://www.mdpi.com/1420-3049/27/22/7799
N2  - 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.
ER  -

KOS, Jiří; Gilles DEGOTTE; Dominika PINDJAKOVA; Tomáš STRHÁRSKY; Timotej JANKECH; Tomáš GONĚC; Pierre FRANCOTTE; Michel FREDERICH and Josef JAMPILEK. Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides. \textit{Molecules}. Basel: MDPI, 2022, vol.~27, No~22, p.~1-10. ISSN~1420-3049. Available from: https://doi.org/10.3390/molecules27227799.

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