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

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

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.

• Language: English
• Keywords: dehydroabietane derivatives, diterpenes, MurA inhibitors, MurF inhibitors, Staphylococcus aureus MurA, Escherichia coli MurA
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 15 str.
• Numbering: Vol. 10, iss. 12, art. 1535
• PID: 20.500.12556/RUL-136941
• UDC: 543.645.7:615.3
• ISSN on article: 2079-6382
• DOI: 10.3390/antibiotics10121535
• COBISS.SI-ID: 98673411
• Publication date in RUL: 25.05.2022

Record is a part of a journal

• Title: Antibiotics
• Shortened title: Antibiotics
• Publisher: MDPI
• ISSN: 2079-6382
• COBISS.SI-ID: 522975769

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 15.12.2021

Secondary language

• Language: Slovenian
• Keywords: derivati dehidroabietana, diterpeni, zaviralci MurA, zaviralci MurF, bakterijske celice, protibakterijsko delovanje, odporni sevi, antibiotiki