Trifluoromethylcinnamanilides Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652079%3A_____%2F25%3A00603309" target="_blank" >RIV/86652079:_____/25:00603309 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/25:00140450 RIV/61989592:15310/25:73626865 RIV/62157124:16170/25:43882577

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0045206824008629?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206824008629?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2024.107957" target="_blank" >10.1016/j.bioorg.2024.107957</a>

Result language

angličtina

Original language name

Trifluoromethylcinnamanilides Effective dual inhibitors of Mycobacterium smegmatis and Plasmodium falciparum

Original language description

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

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LM2023048" target="_blank" >LM2023048: Czech Carbon Observation System</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

1090-2120

Volume of the periodical

154

Issue of the periodical within the volume

JAN

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

22

Pages from-to

107957

UT code for WoS article

001371448500001

EID of the result in the Scopus database

2-s2.0-85210392268