Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 13 March 2020 / Approved: 15 March 2020 / Online: 15 March 2020 (13:12:33 CET)

How to cite: Zhang, J.; Yakovlieva, L.; de Haan, B.J.; de Vos, P.; Minnaard, A.J.; Witte, M.D.; Walvoort, M.T. Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing β Cells. Preprints 2020, 2020030244 (doi: 10.20944/preprints202003.0244.v1). Zhang, J.; Yakovlieva, L.; de Haan, B.J.; de Vos, P.; Minnaard, A.J.; Witte, M.D.; Walvoort, M.T. Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing β Cells. Preprints 2020, 2020030244 (doi: 10.20944/preprints202003.0244.v1).

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 (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.

Subject Areas

antibiotics; β cells; streptozotocin; regioselective oxidation

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