Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10505544" target="_blank" >RIV/00179906:_____/25:10505544 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11160/25:10505544
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=wJ1Goz~sbP" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=wJ1Goz~sbP</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.202500085" target="_blank" >10.1002/cmdc.202500085</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives
Popis výsledku v původním jazyce
A series of 33 (E)-N'-benzylidenepyrazine-2-carbohydrazides and their derivatives were synthesized and tested for biological activity. Benzylidene derivatives with 2-OH substitution on the phenyl ring (18: R = 2-OH, 21: R = 2,3-diOH, and 22: R = 2,4-diOH) exhibit various biological activities. Compounds 18 and 21 demonstrate antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. tuberculosis H37Rv, and M. aurum, with minimum inhibitory concentration values ranging from 15.625 to 62.5 mu g mL-1. Compounds 18, 21, and 22 show mild cytotoxicity on several human cell lines (IC50 ranging from 70.2 to 500 mu M). Crystallographic studies confirm the (E)-configuration of compound 18 and a nearly planar molecular conformation. Due to their structural similarity with salicylaldehyde isonicotinoyl hydrazone (SIH), a known iron chelator, selected compounds were tested for iron-chelating properties, revealing comparable or superior activity. Mechanistic assays targeting enoyl-[acyl carrier protein] reductase (InhA), isocitrate lyase (ICL), and lipid/mycolic acid biosynthesis show no significant inhibition, suggesting a nonspecific mechanism potentially linked to iron chelation. A correlation is observed between chelating activity and cytotoxicity, while antimycobacterial activity appears to involve additional mechanisms. Pharmacokinetic studies with compound 18 reveal no specific plasma metabolites, and no significant metabolites are detected after incubation with human liver microsomes.
Název v anglickém jazyce
Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives
Popis výsledku anglicky
A series of 33 (E)-N'-benzylidenepyrazine-2-carbohydrazides and their derivatives were synthesized and tested for biological activity. Benzylidene derivatives with 2-OH substitution on the phenyl ring (18: R = 2-OH, 21: R = 2,3-diOH, and 22: R = 2,4-diOH) exhibit various biological activities. Compounds 18 and 21 demonstrate antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. tuberculosis H37Rv, and M. aurum, with minimum inhibitory concentration values ranging from 15.625 to 62.5 mu g mL-1. Compounds 18, 21, and 22 show mild cytotoxicity on several human cell lines (IC50 ranging from 70.2 to 500 mu M). Crystallographic studies confirm the (E)-configuration of compound 18 and a nearly planar molecular conformation. Due to their structural similarity with salicylaldehyde isonicotinoyl hydrazone (SIH), a known iron chelator, selected compounds were tested for iron-chelating properties, revealing comparable or superior activity. Mechanistic assays targeting enoyl-[acyl carrier protein] reductase (InhA), isocitrate lyase (ICL), and lipid/mycolic acid biosynthesis show no significant inhibition, suggesting a nonspecific mechanism potentially linked to iron chelation. A correlation is observed between chelating activity and cytotoxicity, while antimycobacterial activity appears to involve additional mechanisms. Pharmacokinetic studies with compound 18 reveal no specific plasma metabolites, and no significant metabolites are detected after incubation with human liver microsomes.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30104 - Pharmacology and pharmacy
Návaznosti výsledku
Projekt
<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2025
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
ChemMedChem
ISSN
1860-7179
e-ISSN
1860-7187
Svazek periodika
20
Číslo periodika v rámci svazku
18
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
10
Strana od-do
202500085
Kód UT WoS článku
001560221300001
EID výsledku v databázi Scopus
2-s2.0-105014462939