Novel Quinazolinones Active against Multidrug-Resistant Mycobacterium Tuberculosis: Synthesis, Antimicrobial Evaluation, and in Silico Exploration of Penicillin-Binding Protein 1A as a Potential Target
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10499788" target="_blank" >RIV/00179906:_____/25:10499788 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11160/25:10499788
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=BWYhXnXDmR" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=BWYhXnXDmR</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.202500147" target="_blank" >10.1002/cmdc.202500147</a>
Alternative languages
Result language
angličtina
Original language name
Novel Quinazolinones Active against Multidrug-Resistant Mycobacterium Tuberculosis: Synthesis, Antimicrobial Evaluation, and in Silico Exploration of Penicillin-Binding Protein 1A as a Potential Target
Original language description
Quinazolinone derivatives have emerged as promising scaffolds in antimicrobial drug discovery. This work focuses on the design, synthesis, and evaluation of novel quinazolinone-based compounds and predicts their potential to interact with mycobacterial penicillin-binding proteins (PBPs). Relying on established structure-activity relationships of antibacterial quinazolinones, a total of 53 compounds belonging to three different structural types are synthesized and biologically evaluated for antimycobacterial, antibacterial, and antifungal activities. Biological evaluations reveal selective efficacy against Mycobacterium tuberculosis with minimum inhibitory concentrations (MICs) as low as 6.25 mu g mL-1 for some derivatives, and this activity is preserved against drug-resistant strains. Molecular docking studies suggest a potential allosteric binding site in mycobacterial PBP 1A (PonA1, UniProt ID: P71707), and subsequential molecular dynamics confirm stable binding with key stabilizing interaction between the carbonyl oxygen of the quinazolinone and either ARG399 or ASP474. These findings suggest quinazolinone derivatives as viable candidates for further development as non-beta-lactam PBP inhibitors, addressing the urgent need for new antitubercular therapies.
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
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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
13
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
e202500147
UT code for WoS article
001507990500001
EID of the result in the Scopus database
2-s2.0-105006847508