Substituted N-phenylitaconamides as inhibitors of mycobacteria and mycobacterial isocitrate lyase Context Sensitive Links 1 of 2 Substituted N-phenylitaconamides as inhibitors of mycobacteria and mycobacterial isocitrate lyase

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F71009396%3A_____%2F22%3AN0000010" target="_blank" >RIV/71009396:_____/22:N0000010 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0928098722001373?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0928098722001373?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejps.2022.106252" target="_blank" >10.1016/j.ejps.2022.106252</a>

Result language

angličtina

Original language name

Substituted N-phenylitaconamides as inhibitors of mycobacteria and mycobacterial isocitrate lyase Context Sensitive Links 1 of 2 Substituted N-phenylitaconamides as inhibitors of mycobacteria and mycobacterial isocitrate lyase

Original language description

Novel antimycobacterial drugs are needed, especially those with dual activity against both actively growing and non-replicating subpopulations of mycobacteria. Isocitrate lyase (ICL) is one of proposed targets and this enzyme is inhibited by itaconic acid. That is why we have designed and prepared sixteen amides of itaconic acid and various anilines and amine antimicrobial drugs to evaluate them as potential inhibitors of ICL and antimycobacterial agents. N-Phenylitaconamides were prepared from itaconic anhydride and substituted anilines (yields 57-99%). They were characterized and evaluated against mycobacterial ICL and against actively growing mycobacteria (M. tuberculosis H37Rv, M. avium, two strains of M. kansasii). All derivatives showed antimycobacterial efficacy with minimum inhibitory concentrations starting from 125 mu M. M. kansasii was the most susceptible species. Itaconamides derived from sulfonamides or p-aminosalicylic acid were optimal for activity against extracellular mycobacteria. ICL1 was significantly inhibited by two compounds, with 2-methylene-4-[(4nitrophenyl)amino]-4-oxobutanoic acid 1k being the most potent (36% inhibition at 10 mu M), which was also more efficient than two comparators. Molecular docking revealed its mode of binding to the enzyme. Using in silico tools, physicochemical properties and structural features for drug-likeness and gastrointestinal absorption were evaluated.

Czech name

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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

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GJ20-19638Y" target="_blank" >GJ20-19638Y: Design and investigation of novel antimicrobial agents active against drug-resistant and biofilm-forming gram-positive bacteria</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

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

Name of the periodical

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

e-ISSN

1879-0720

Volume of the periodical

176

Issue of the periodical within the volume

106252

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

8

Pages from-to

1-8

UT code for WoS article

000839196000010

EID of the result in the Scopus database

2-s2.0-85134358236