Synthesis and antibacterial activities of baulamycin A inspired derivatives

Namkyoung Kim, Sandip Sengupta, Jiwon Lee, Uttam Dash, Soojeung Kim, Hak Joong Kim, Chiman Song, Taebo Sim

Research output: Contribution to journalArticlepeer-review

Abstract

SbnE is an essential enzyme for staphyloferrin B biosynthesis in Staphylococcus aureus. An earlier study showed that natural product baulamycin A has in vitro inhibitory activity against SbnE and antibacterial potency. A SAR study with analogues of baulamycin A was conducted to identify potent inhibitors of SbnE and/or effective antibiotics against MRSA. The results show that selected analogues, including 11, 18, 21, 24a, 24c, 24m and 24n, exhibit single-digit micromolar inhibitory potencies against SbnE (IC50s = 1.81–8.94 μM) and 11, 24m, 24n possess significant activities against both SbnE (IC50s = 4.12–6.12 μM) and bacteria (MICs = 4–32 μg/mL). Biological investigations revealed that these substances possess potent cell wall disruptive activities and that they inhibit siderophore production in MRSA. Among the selected analogues, 7 has excellent antibiotic activities both gram-positive and –negative bacteria (0.5–4 μg/mL). Moreover, these analogues significantly impede biofilm formation in a concentration-dependent manner. Taken together, the results of the investigation provide valuable insight into the nature of novel baulamycin A analogues that have potential efficacy against MRSA owing to their membrane damaging activity and/or inhibitory efficacy against siderophore production.

Original languageEnglish
Article number115592
JournalEuropean Journal of Medicinal Chemistry
Volume259
DOIs
Publication statusPublished - 2023 Nov 5

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Masson SAS

Keywords

  • Baulamycin A
  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • SbnE
  • Siderophore

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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