Trifluoromethylcinnamanilides - Effective dual inhibitors of
Mycobacterium smegmatis and Plasmodium falciparum

J 2025

Trifluoromethylcinnamanilides - Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum

KOS, Jiří; Tomáš STRHÁRSKY; Rodrigo TOSSO; Lucas GUTIERREZ; Dominika KOS et al.

Základní údaje

Originální název

Trifluoromethylcinnamanilides - Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum

Autoři

Vydání

Bioorganic Chemistry, SAN DIEGO, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025, 0045-2068

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30107 Medicinal chemistry

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.700 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00140450

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Cinnamanilides; Lipophilicity; P. falciparum; Cytotoxicity; Molecular modeling; QTAIM calculations

Štítky

14110512, 14110516, podil, rivok, ÚChL, ÚMF

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 3. 2026 13:32, Mgr. Tereza Miškechová

Anotace

V originále

A series of eighteen new 2-trifluoromethylcinnamanilides (1a-r) were synthesized by microwave synthesis and investigated for their antimycobacterial and antimalarial activities, along with the complementary (2E)-3-[3(trifluoromethyl)phenyl]-N-arylprop-2-enanilides (2a-r) and (2E)-3-[4-(trifluoromethyl)phenyl]-N-arylprop-2enanilides (3a-r) prepared earlier. All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102. The most active compounds against M. smegmatis (MIC values in the range of 1.17-11.1 mu M, more effective than rifampicin) were anilides substituted by 3,5-CF3 (1q, 2q, 3q), 4-OCF3 (1k), and 4-CF3 (1j, 2j). The most effective agents against P. falciparum (IC50 values in the range of 0.32-4.5 mu M, comparable to chloroquine) were anilides substituted by 3,5-CF3 (1q, 2q, 3q), 2-Br-4-OCF3 (1r), 4-CF3 (1j, 3j), 4-F (2d), 4-Cl (2g), 2-Cl (1e, 2e). A preliminary in vitro cytotoxicity screening was assessed using human leukemic cell lines and human dermal fibroblasts, revealing the toxic effect of 3,5-CF3 substituted anilides. On the other hand, the other investigated agents showed insignificant cytotoxic effects. Stability assays using rat liver microsomes demonstrated that compounds 1r (R = 2-Br-4-OCF3) and 1q (R = 3,5-CF3) are neither metabolized nor affect cytochrome P450 metabolizing capacity in vitro. Furthermore, complex in silico studies were performed - a combined approach (docking/MD simulations/QTAIM calculations) helped to define the molecular interactions that were applied during the binding of active agents and the subsequent inhibition of their molecular targets - InhA (activity against M. smegmatis) and arginase

Návaznosti

90248, velká výzkumná infrastruktura

Název: CzeCOS IV

Citovat

KOS, Jiří; Tomáš STRHÁRSKY; Rodrigo TOSSO; Lucas GUTIERREZ; Dominika KOS; Jan JUŘICA; Ondřej ZENDULKA; Ondřej PEŠ; Jana GREGOROVÁ; Gilles DEGOTTE; Tomáš GONĚC; Michal ORAVEC; Veronika VOJACKOVA; Vladimir KRYSTOF; Alois ČÍŽEK; Pierre FRANCOTTE; Michel FREDERICH; Josef JAMPÍLEK a Daniel ENRIZ. Trifluoromethylcinnamanilides - Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum. Bioorganic Chemistry. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025, roč. 154, January 2025, s. 1-22. ISSN 0045-2068. Dostupné z: https://doi.org/10.1016/j.bioorg.2024.107957.

@article{2464204,
   author = {Kos, Jiří and Strhársky, Tomáš and Tosso, Rodrigo and Gutierrez, Lucas and Kos, Dominika and Juřica, Jan and Zendulka, Ondřej and Peš, Ondřej and Gregorová, Jana and Degotte, Gilles and Goněc, Tomáš and Oravec, Michal and Vojackova, Veronika and Krystof, Vladimir and Čížek, Alois and Francotte, Pierre and Frederich, Michel and Jampílek, Josef and Enriz, Daniel},
   article_location = {SAN DIEGO},
   article_number = {January 2025},
   doi = {https://doi.org/10.1016/j.bioorg.2024.107957},
   keywords = {Cinnamanilides; Lipophilicity; P. falciparum; Cytotoxicity; Molecular modeling; QTAIM calculations},
   language = {eng},
   issn = {0045-2068},
   journal = {Bioorganic Chemistry},
   title = {Trifluoromethylcinnamanilides - Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum},
   url = {https://www.sciencedirect.com/science/article/abs/pii/S0045206824008629?via%3Dihub},
   volume = {154},
   year = {2025}
}

TY  - JOUR
ID  - 2464204
AU  - Kos, Jiří - Strhársky, Tomáš - Tosso, Rodrigo - Gutierrez, Lucas - Kos, Dominika - Juřica, Jan - Zendulka, Ondřej - Peš, Ondřej - Gregorová, Jana - Degotte, Gilles - Goněc, Tomáš - Oravec, Michal - Vojackova, Veronika - Krystof, Vladimir - Čížek, Alois - Francotte, Pierre - Frederich, Michel - Jampílek, Josef - Enriz, Daniel
PY  - 2025
TI  - Trifluoromethylcinnamanilides - Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum
JF  - Bioorganic Chemistry
VL  - 154
IS  - January 2025
SP  - 1-22
EP  - 1-22
PB  - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN  - 00452068
KW  - Cinnamanilides
KW  - Lipophilicity
KW  - P. falciparum
KW  - Cytotoxicity
KW  - Molecular modeling
KW  - QTAIM calculations
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0045206824008629?via%3Dihub
N2  - A series of eighteen new 2-trifluoromethylcinnamanilides (1a-r) were synthesized by microwave synthesis and investigated for their antimycobacterial and antimalarial activities, along with the complementary (2E)-3-[3(trifluoromethyl)phenyl]-N-arylprop-2-enanilides (2a-r) and (2E)-3-[4-(trifluoromethyl)phenyl]-N-arylprop-2enanilides (3a-r) prepared earlier. All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102. The most active compounds against M. smegmatis (MIC values in the range of 1.17-11.1 mu M, more effective than rifampicin) were anilides substituted by 3,5-CF3 (1q, 2q, 3q), 4-OCF3 (1k), and 4-CF3 (1j, 2j). The most effective agents against P. falciparum (IC50 values in the range of 0.32-4.5 mu M, comparable to chloroquine) were anilides substituted by 3,5-CF3 (1q, 2q, 3q), 2-Br-4-OCF3 (1r), 4-CF3 (1j, 3j), 4-F (2d), 4-Cl (2g), 2-Cl (1e, 2e). A preliminary in vitro cytotoxicity screening was assessed using human leukemic cell lines and human dermal fibroblasts, revealing the toxic effect of 3,5-CF3 substituted anilides. On the other hand, the other investigated agents showed insignificant cytotoxic effects. Stability assays using rat liver microsomes demonstrated that compounds 1r (R = 2-Br-4-OCF3) and 1q (R = 3,5-CF3) are neither metabolized nor affect cytochrome P450 metabolizing capacity in vitro. Furthermore, complex in silico studies were performed - a combined approach (docking/MD simulations/QTAIM calculations) helped to define the molecular interactions that were applied during the binding of active agents and the subsequent inhibition of their molecular targets - InhA (activity against M. smegmatis) and arginase
ER  -

KOS, Jiří; Tomáš STRHÁRSKY; Rodrigo TOSSO; Lucas GUTIERREZ; Dominika KOS; Jan JUŘICA; Ondřej ZENDULKA; Ondřej PEŠ; Jana GREGOROVÁ; Gilles DEGOTTE; Tomáš GONĚC; Michal ORAVEC; Veronika VOJACKOVA; Vladimir KRYSTOF; Alois ČÍŽEK; Pierre FRANCOTTE; Michel FREDERICH; Josef JAMPÍLEK a Daniel ENRIZ. Trifluoromethylcinnamanilides - Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum. \textit{Bioorganic Chemistry}. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2025, roč.~154, January 2025, s.~1-22. ISSN~0045-2068. Dostupné z: https://doi.org/10.1016/j.bioorg.2024.107957.

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