Maja Kokot (Avtor), Matjaž Weiss (Avtor), Irena Zdovc (Avtor), Martina Hrast (Avtor), Marko Anderluh (Avtor), Nikola Minovski (Avtor)

Povzetek

We designed and synthesized an optimized library of novel bacterial topoisomerase inhibitors with p-halogenated phenyl right-hand side fragments and significantly enhanced and balanced dual-targeted DNA gyrase and topoisomerase IV activities of Staphylococcus aureus and Escherichia coli. By increasing the electron-withdrawing properties of the p-halogenated phenyl right-hand side fragment and maintaining a similar lipophilicity and size, an increased potency was achieved, indicating that the antibacterial activities of this series of novel bacterial topoisomerase inhibitors against all target enzymes are determined by halogen-bonding rather than van der Waals interactions. They show nanomolar enzyme inhibitory and whole-cell antibacterial activities against S. aureus and methicillin-resistant S. aureus (MRSA) strains. However, due to the relatively high substrate specificity for the bacterial efflux pumps, they tend to be less potent against E. coli and other Gram-negative pathogens.

Ključne besede

NBTIs;DNA gyrase;topoisomerase IV;bifurcated halogen bonds;dual targeting;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.4:54:579
COBISS: 73185027 Povezava se bo odprla v novem oknu
ISSN: 1948-5875
Št. ogledov: 3
Št. prenosov: 0
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Angleški jezik
Sekundarne ključne besede: Farmacevtska kemija;Patogeni;Encimska aktivnost;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1478-1485
Letnik: ǂVol. ǂ12
Zvezek: ǂiss. ǂ9
Čas izdaje: 2021
DOI: 10.1021/acsmedchemlett.1c00345
ID: 16608113