Structurally optimized potent dual-targeting NBTI antibacterials with an enhanced bifurcated halogen-bonding propensity

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

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.

• Jezik: Angleški jezik
• Ključne besede: NBTIs, DNA gyrase, topoisomerase IV, bifurcated halogen bonds, dual targeting
• 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: Str. 1478-1485
• Številčenje: Vol. 12, iss. 9
• PID: 20.500.12556/RUL-141453
• UDK: 615.4:54:579
• ISSN pri članku: 1948-5875
• DOI: 10.1021/acsmedchemlett.1c00345
• COBISS.SI-ID: 73185027
• Datum objave v RUL: 29.09.2022

Gradivo je del revije

• Naslov: ACS medicinal chemistry letters
• Založnik: American Chemical Society
• ISSN: 1948-5875
• COBISS.SI-ID: 2959217

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.