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