Hybrid inhibitors of DNA gyrase A and B : design, synthesis and evaluation

Durcik, Martina (avtor), Skok, Žiga (avtor), Ilaš, Janez (avtor), Zidar, Nace (avtor), Zega, Anamarija (avtor), Szili, Petra (avtor), Draskovits, Gábor (avtor), Revesz, T. (avtor), Kikelj, Danijel (avtor), Nyerges, Ákos (avtor), Pál, Csaba (avtor), Peterlin-Mašič, Lucija (avtor), Tomašič, Tihomir (avtor)

The discovery of multi-targeting ligands of bacterial enzymes is an important strategy to combat rapidly spreading antimicrobial resistance. Bacterial DNA gyrase and topoisomerase IV are validated targets for the development of antibiotics. They can be inhibited at their catalytic sites or at their ATP binding sites. Here we present the design of new hybrids between the catalytic inhibitor ciprofloxacin and ATP-competitive inhibitors that show low nanomolar inhibition of DNA gyrase and antibacterial activity against Gram-negative pathogens. The most potent hybrid 3a has MICs of 0.5 µg/mL against Klebsiella pneumoniae, 4 µg/mL against Enterobacter cloacae, and 2 µg/mL against Escherichia coli. In addition, inhibition of mutant E. coli strains shows that these hybrid inhibitors interact with both subunits of DNA gyrase (GyrA, GyrB), and that binding to both of these sites contributes to their antibacterial activity.

• Jezik: Angleški jezik
• Ključne besede: antibacterial, ciprofloxacin, DNA gyrase, dual inhibitor, hybrid
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 17 str.
• Številčenje: Vol. 13, iss. 1, art. 6
• PID: 20.500.12556/RUL-134779
• UDK: 615.4:54:615.015.8
• ISSN pri članku: 1999-4923
• DOI: 10.3390/pharmaceutics13010006
• COBISS.SI-ID: 44007939
• Datum objave v RUL: 01.02.2022

Gradivo je del revije

• Naslov: Pharmaceutics
• Skrajšan naslov: Pharmaceutics
• Založnik: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.01.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: DNK giraze, ciprofloksacin, zaviralci, hibridi, bakterijska rezistenca, farmacevtska kemija