Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11160/25:10505544
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Investigating the Mechanism of Antimycobacterial and Antiproliferative Activity of (E)-N'-Benzylidenepyrazine-2-Carbohydrazides and their Derivatives
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ChemMedChem
ISSN
1860-7179
e-ISSN
1860-7187
Volume of the periodical
20
Issue of the periodical within the volume
18
Country of publishing house
DE - GERMANY
Number of pages
10
Pages from-to
202500085
UT code for WoS article
001560221300001
EID of the result in the Scopus database
2-s2.0-105014462939