Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
Molecules. 2018 Apr 13;23(4):899. doi: 10.3390/molecules23040899.
As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 , , and species. We also evaluate their impact on the hemolysis of murine erythrocytes and the cytotoxicity against mammalian cell lines. While the triazole linker appears to confer optimal activity overall, all of the linkers incorporated into the TOB derivatives resulted in compounds that are very effective against the species, with MIC values ranging from 0.48 to 3.9 μg/mL.
随着与真菌感染相关的威胁持续增加，抗真菌药物的供应仍然令人担忧，很明显，急需增强抗真菌武器库。基于我们之前发现的具有抗真菌活性的妥布霉素（TOB）衍生物，我们进一步研究了各种连接子对这些氨基糖苷类药物生物活性的影响。在此，我们分析了硫醚、砜、三唑、酰胺和醚官能团如何影响烷基化 TOB 衍生物对 22 种、、和 种真菌的抗真菌活性。我们还评估了它们对鼠红细胞溶血和对哺乳动物细胞系细胞毒性的影响。虽然三唑连接子似乎总体上赋予了最佳的活性，但所有被整合到 TOB 衍生物中的连接子都产生了对 种真菌非常有效的化合物，其 MIC 值范围为 0.48 至 3.9 μg/mL。
