Maja Kokot (Avtor), Martina Hrast (Avtor), Lipeng Feng (Avtor), Lesley A Mitchenall (Avtor), David M. Lawson (Avtor), Anthony Maxwell (Avtor), Tanya Parish (Avtor), Nikola Minovski (Avtor), Marko Anderluh (Avtor)

Povzetek

In this Letter, we present a small series of novel bacterial topoisomerase inhibitors (NTBIs) that exhibit both potent inhibition of Mycobacterium tuberculosis DNA gyrase and potent antimycobacterial activity. The disclosed crystal structure of M. tuberculosis DNA gyrase in complex with DNA and compound 5 from this NBTI series reveals the binding mode of an NBTI in the GyrA binding pocket and confirms the presence and importance of halogen bonding for the excellent on-target potency. In addition, we have shown that compound 5 is a promising M. tuberculosis DNA gyrase inhibitor, with an IC50 for M. tuberculosis gyrase of 0.096 μM, and it has potent activity against M. tuberculosis, with an IC50 of 0.165 μM.

Ključne besede

DNA giraza;Mycobacterium tuberculosis;inhibitorji;bakterijske topoizomeraze;NBTIs;DNA gyrase;M. tuberculosis;crystal structure;bifurcated halogen bonds;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 615.4:54:616-002.5
COBISS: 215946755 Povezava se bo odprla v novem oknu
ISSN: 1948-5875
Št. ogledov: 30
Št. prenosov: 15
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: Farmacevtska kemija;Tuberkuloza;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 2164-2170
Letnik: ǂVol. ǂ15
Zvezek: ǂiss. ǂ12
Čas izdaje: 2024
DOI: 10.1021/acsmedchemlett.4c00447
ID: 25518678