Maja Kokot (Avtor), Matjaž Weiss (Avtor), Irena Zdovc (Avtor), L. Šenerović (Avtor), Natasa Radakovic (Avtor), Marko Anderluh (Avtor), Nikola Minovski (Avtor), Martina Hrast (Avtor)

Povzetek

Novel bacterial topoisomerase inhibitors (NBTIs) are new promising antimicrobials for the treatment of multidrug-resistant bacterial infections. In recent years, many new NBTIs have been discovered, however most of them struggle with the same issue - the balance between antibacterial activity and hERG-related toxicity. We started a new campaign by optimizing the previous series of NBTIs, followed by the design and synthesis of a new, amide-containing focused NBTI library to reduce hERG inhibition and maintain antibacterial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This optimization strategy yielded the lead compound 12 that exhibits potent antibacterial activity against Gram-positive bacteria, reduced hERG inhibition, no cardiotoxicity in zebrafish model, and a favorable in vivo efficacy in a neutropenic murine thigh infection model of MRSA infection.

Ključne besede

DNA giraza;topoizomeraza IV;antibakterijska zdravila;inhibicija;učinkovitost in vivo;NBTIs;DNA gyrase;Topoisomerase IV;antibacterials;MRSA;hERG inhibition;in vivo efficacy;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.28
COBISS: 141418755 Povezava se bo odprla v novem oknu
ISSN: 0223-5234
Št. ogledov: 255
Št. prenosov: 31
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: Slovenski jezik
Sekundarne ključne besede: Bakterije;Farmacevtska kemija;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-13
Zvezek: ǂVol. ǂ250
Čas izdaje: 2023
DOI: 10.1016/j.ejmech.2023.115160
ID: 17994510