Research Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK.
Sci Rep. 2018 Jan 18;8(1):1150. doi: 10.1038/s41598-017-18948-w.
Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These results suggest that methyl disulfides are novel scaffolds which could lead to the development of new drugs against tuberculosis (TB).
先前有报道称，来自葱属植物的二硫键（通常被称为波斯葱）具有抗菌特性。这些化合物的类似物通过 S-甲基化适当的硫醇并用 S-甲基甲硫磺酸酯进行 S-甲基硫代化产生，表现出抗菌活性，一种化合物在 17µM（4mg/L）时抑制结核分枝杆菌的生长，其他化合物在 32-138µM（8-32mg/L）的浓度范围内抑制大肠杆菌和耐多药（MDR）金黄色葡萄球菌的生长。这些化合物对克雷伯菌和变形杆菌属也表现出中等抑制作用。采用全细胞表型生物测定法，如斑点培养生长抑制测定法（SPOTi）、药物外排抑制、生物膜抑制和细胞毒性测定法来评估这些化合物。值得注意的是，它们能够抑制分枝杆菌药物外排和生物膜形成，同时对结核分枝杆菌 H37Rv 保持高选择性。这些结果表明，二甲基二硫醚是新型支架，可能会开发出针对结核病（TB）的新药。
