Department of Pharmaceutical Technology and Biochemistry and BioTechMed Centre, Gdańsk University of Technology, 80-233 Gdańsk, Poland.
Department of Organic Chemistry and BioTechMed Centre, Gdańsk University of Technology, 80-233 Gdańsk, Poland.
Molecules. 2021 Sep 8;26(18):5475. doi: 10.3390/molecules26185475.
A molecular umbrella composed of two -sulfated cholic acid residues was applied for the construction of conjugates with cispentacin, containing a "trimethyl lock" (TML) or -dithiobenzylcarbamoyl moiety as a cleavable linker. Three out of five conjugates demonstrated antifungal in vitro activity against and but not against , with MIC values in the 0.22-0.99 mM range and were not hemolytic. Antifungal activity of the most active conjugate , containing the TML-pimelate linker, was comparable to that of intact cispentacin. A structural analogue of , containing the Nap-NH fluorescent probe, was accumulated in cells, and TML-containing conjugates were cleaved in cell-free extract of cells. These results suggest that a molecular umbrella can be successfully applied as a nanocarrier for the construction of cleavable antifungal conjugates.
一种由两个磺酸胆酸残基组成的分子伞被应用于与 cis -戊烯二酮（cispentacin）形成轭合物，其中包含“三甲基锁”（TML）或 -二硫代苯甲酰基氨基甲酰基部分作为可裂解的连接子。五种轭合物中有三种对 和 具有体外抗真菌活性，但对 没有活性，MIC 值在 0.22-0.99 mM 范围内，且没有溶血作用。含有 TML-壬酸酯连接子的最活性轭合物 的抗真菌活性与完整的 cis -戊烯二酮相当。一种含有 Nap-NH 荧光探针的 结构类似物在 细胞中积累，并且 TML 含有轭合物在 细胞的无细胞提取物中被裂解。这些结果表明，分子伞可以成功地用作构建可裂解抗真菌轭合物的纳米载体。
