Inhibition of MurA enzyme from Escherichia coli and Staphylococcus aureus by diterpenes from Lepechinia meyenii and their synthetic analogs

Funes Chabán, Macarena (avtor), Hrast, Martina (avtor), Frlan, Rok (avtor), Graikioti, Dafni G. (avtor), Athanassopoulos, Constantinos M. (avtor), Carpinella, María Cecilia (avtor)

Enzymes MurA and MurF, involved in bacterial cell wall synthesis, have been validated as targets for the discovery of novel antibiotics. A panel of plant-origin antibacterial diterpenes and synthetic analogs derived therefrom were investigated for their inhibitory properties on these enzymes from Escherichia coli and Staphylococcus aureus. Six compounds were proven to be effective for inhibiting MurA from both bacteria, with IC$_{50}$ values ranging from 1.1 to 25.1 µM. To further mechanistically investigate the nature of binding and to explain the activity, these compounds were docked into the active site of MurA from E. coli. The aromatic ring of the active compounds showed a T-shaped π–π interaction with the phenyl ring of Phe328, and at least one hydrogen bond was formed between the hydroxy groups and Arg120 and/or Arg91. The results disclosed here establish new chemical scaffolds for the development of novel entities targeting MurA as potential antibiotics to combat the threat of pathogenic bacteria, particularly resistant strains.

• Jezik: Angleški jezik
• Ključne besede: dehydroabietane derivatives, diterpenes, MurA inhibitors, MurF inhibitors, Staphylococcus aureus MurA, Escherichia coli MurA
• 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: 15 str.
• Številčenje: Vol. 10, iss. 12, art. 1535
• PID: 20.500.12556/RUL-136941
• UDK: 543.645.7:615.3
• ISSN pri članku: 2079-6382
• DOI: 10.3390/antibiotics10121535
• COBISS.SI-ID: 98673411
• Datum objave v RUL: 25.05.2022

Gradivo je del revije

• Naslov: Antibiotics
• Skrajšan naslov: Antibiotics
• Založnik: MDPI
• ISSN: 2079-6382
• COBISS.SI-ID: 522975769

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: 15.12.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: derivati dehidroabietana, diterpeni, zaviralci MurA, zaviralci MurF, bakterijske celice, protibakterijsko delovanje, odporni sevi, antibiotiki