Antibacterial 3,6-Disubstituted 4-Hydroxy-5,6-dihydro-2H-pyran-2-ones from Serratia plymuthica MF371-2

Sammanfattning

Bioassay-guided fractionation of culture extracts of Serratia plymuthica strain MF371-2 resulted in the isolation of two new antibacterial compounds with potent activity against Gram-positive bacteria, including Staphylococcus aureus LMG 15975 (MRSA). A spectroscopic investigation, in combination with synthesis, enabled the characterization of the compounds as 3-butyryl-4-hydroxy-6-heptyl-5,6-dihydro2H-pyran-2-one (plymuthipyranone A, 1) and 3-butyry1-4-hydroxy-6-nony1-5,6-dihydro-2H-pyran-2-one (plymuthipyranone B, 2). The MIC values for 1 and 2 against S. aureus LMG 15975 were determined to be 1-2 mu g mL(-1) and 0.8 mu g mL(-1), respectively. Compound 2 was found to have potent activity against many strains of S. aureus, including several mupirocin-resistant strains, other species of Staphylococcus, and vancomycin-resistant enterococci. Compound 2 was slightly cytotoxic for human cells, with CC50 values between 4.7 and 40 mu g mL(-1), but the CC50/MIC ratio was >= 10 for many tested combinations of human cells and bacteria, suggesting its possible use as an antibacterial agent. Several analogues were synthesized with different alkyl groups in the 3- and 6-positions (6-13), and their biological properties were evaluated. It was concluded that the activity of the compounds increased with the lengths of the alkyl and acyl substituents.

Publicerad i

Journal of Natural Products
2017, volym: 80, nummer: 11, sidor: 2997-3002
Utgivare: AMER CHEMICAL SOC

SLU författare

• Bjerketorp, Joakim

  • Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
    

• Levenfors, Jolanta

  • Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
    

• Nord, Christina

  • Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
    

• Andersson, Pierre

  • Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
    

• Guss, Bengt

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Broberg, Anders

  • Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
    

Associerade SLU-program

AMR: Bakterier

UKÄ forskningsämne

Jordbruksvetenskap

Publikationens identifierare

• DOI: https://doi.org/10.1021/acs.jnatprod.7b00565

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/92694