Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00478148" target="_blank" >RIV/61388963:_____/17:00478148 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/17:10365149 RIV/00179906:_____/17:10365149 RIV/71009396:_____/17:N0000010

Výsledek na webu

<a href="http://dx.doi.org/10.1002/ardp.201700020" target="_blank" >http://dx.doi.org/10.1002/ardp.201700020</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ardp.201700020" target="_blank" >10.1002/ardp.201700020</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

Popis výsledku v původním jazyce

A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 mu mol/L than 3-nitropropionic acid, a standard inhibitor. The compounds were also found to act as exogenous chelators of iron, which is an obligate cofactor for many mycobacterial enzymes. Due to their low cytotoxicity, together with the activity against isocitrate lyase and the ability to sequester iron ions, the compounds belong to potential antibiotics with the main effect on mycobacteria.

Název v anglickém jazyce

Design, Synthesis, and Biological Evaluation of Isothiosemicarbazones with Antimycobacterial Activity

Popis výsledku anglicky

A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 mu mol/L than 3-nitropropionic acid, a standard inhibitor. The compounds were also found to act as exogenous chelators of iron, which is an obligate cofactor for many mycobacterial enzymes. Due to their low cytotoxicity, together with the activity against isocitrate lyase and the ability to sequester iron ions, the compounds belong to potential antibiotics with the main effect on mycobacteria.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Archiv der Pharmazie

ISSN

0365-6233

e-ISSN

—

Svazek periodika

350

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000406714000003

EID výsledku v databázi Scopus

2-s2.0-85021182451