Synthesis of 2,3,6-trideoxy sugar triazole hybrids as potential new broad spectrum antimicrobial agents

•Modeled 2,3,6-trideoxy sugar-triazoles as broad-spectrum antibacterial/antifungals.•Novelty of chemistry is in simple reactions leading to desired products.•Some compounds showed antibacterial/antifungal profile comparable to standard drugs.•Compounds' antibacterial activity may be mediated via penicillin binding protein-2.•Compounds showed no toxicity to mammalian cell line L929.

Here, we describe a molecular hybridization inspired design and synthesis of novel 6-triazolyl 2,3,6-trideoxy sugars as promising new broad-spectrum antimicrobial agents using click chemistry in key step. These compounds showed MIC between 0.39 and 50 μg/mL against different native and resistant bacteria and fungi with no toxicity. Among them, compound 29 was the most active molecule with MIC 0.78 μg/mL against Staphylococcus aureus and Klebsiella pneumoniae and 3.12 μg/mL against methicillin- and vancomycin-resistant S. aureus. Compound 26 was the most potent anti-fungal candidate with MIC 0.39 μg/mL against Trichophyton mentagrophytes. Compound 46 was found to be promising with broad-spectrum activity against both bacterial and fungal strains. The bioinformatic studies involving bacteria's protein co-crystals prompted penicillin binding protein-2 as the most likely target of these compounds.

Graphical abstractSchematic depiction of design and synthesis of novel 6-triazolyl 2,3,6-trideoxy sugars as promising new broad-spectrum antimicrobial agents using click chemistry in key step.Figure optionsDownload full-size imageDownload as PowerPoint slide