Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing β Cells

Ji Zhang, Liubov Yakovlieva, Bart J de Haan, Paul de Vos, Adriaan J Minnaard, Martin D Witte, Marthe T C Walvoort*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
79 Downloads (Pure)

Abstract

With the increasing resistance of bacteria to current antibiotics, novel compounds are urgently needed to treat bacterial infections. Streptozotocin (STZ) is a natural product that has broad-spectrum antibiotic activity, albeit with limited use because of its toxicity to pancreatic β cells. In an attempt to derivatize STZ through structural modification at the C3 position, we performed the synthesis of three novel STZ analogues by making use of our recently developed regioselective oxidation protocol. Keto-STZ (2) shows the highest inhibition of bacterial growth (minimum inhibitory concentration (MIC) and viability assays), but is also the most cytotoxic compound. Pre-sensitizing the bacteria with GlcNAc increased the antimicrobial effect, but did not result in complete killing. Interestingly, allo-STZ (3) revealed moderate concentration-dependent antimicrobial activity and no cytotoxicity towards β cells, and deoxy-STZ (4) showed no activity at all.

Original languageEnglish
Article number182
Number of pages11
JournalAntibiotics
Volume9
Issue number4
DOIs
Publication statusPublished - Apr-2020

Keywords

  • antibiotics
  • regioselective oxidation
  • streptozotocin
  • beta cells
  • REGIOSELECTIVE OXIDATION
  • MECHANISMS
  • PHOSPHOENOLPYRUVATE
  • TRANSPORT
  • TOXICITY
  • ANALOGS

Cite this