当前位置：
X-MOL 学术
›
RSC Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Scaffold diversity for enhanced activity of glycosylated inhibitors of fungal adhesion
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-08-17 , DOI: 10.1039/d0md00224k Harlei Martin 1 , Tara Somers 2 , Mathew Dwyer 2 , Ryan Robson 3 , Frederick M Pfeffer 3 , Ragnar Bjornsson 4 , Tobias Krämer 1, 5 , Kevin Kavanagh 2, 6 , Trinidad Velasco-Torrijos 1, 6
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-08-17 , DOI: 10.1039/d0md00224k Harlei Martin 1 , Tara Somers 2 , Mathew Dwyer 2 , Ryan Robson 3 , Frederick M Pfeffer 3 , Ragnar Bjornsson 4 , Tobias Krämer 1, 5 , Kevin Kavanagh 2, 6 , Trinidad Velasco-Torrijos 1, 6
Affiliation
|
Candida albicans is one of the most prevalent fungal pathogens involved in hospital acquired infections. It binds to glycans at the surface of epithelial cells and initiates infection. This process can be blocked by synthetic carbohydrates that mimic the structure of cell surface glycans. Herein we report the evaluation of a series of divalent glycosides featuring aromatic (benzene, squaramide) and bicyclic aliphatic (norbornene) scaffolds, with the latter being the first examples of their kind as small molecule anti-adhesion glycoconjugates. Galactosides 1 and 6, built on an aromatic core, were most efficient inhibitors of adhesion of C. albicans to buccal epithelial cells, displacing up to 36% and 48%, respectively, of yeast already attached to epithelial cells at 138 μM. Remarkably, cis-endo-norbornene 21 performed comparably to benzene-core derivatives. Conformational analysis reveals a preference for compounds 1 and 21 to adopt folded conformations. These results highlight the potential of norbornenes as a new class of aliphatic scaffolds for the synthesis of anti-adhesion compounds.
中文翻译：
用于增强真菌粘附糖基化抑制剂活性的支架多样性
白色念珠菌是与医院获得性感染有关的最普遍的真菌病原体之一。它与上皮细胞表面的聚糖结合并引发感染。这个过程可以被模拟细胞表面聚糖结构的合成碳水化合物阻断。在这里，我们报告了对一系列具有芳香族（苯、方酸酰胺）和双环脂肪族（降冰片烯）支架的二价糖苷的评估，后者是此类小分子抗粘附糖缀合物的第一个例子。半乳糖苷1和6建立在芳香核心之上，是白色念珠菌粘附最有效的抑制剂在 138 μM 的浓度下，分别置换高达 36% 和 48% 的已经附着在上皮细胞上的酵母。值得注意的是，顺式-内-降冰片烯21的性能与苯核心衍生物相当。构象分析揭示了化合物1和21倾向于采用折叠构象。这些结果突出了降冰片烯作为合成抗粘附化合物的新型脂肪族支架的潜力。
更新日期：2020-08-17
中文翻译：
用于增强真菌粘附糖基化抑制剂活性的支架多样性
白色念珠菌是与医院获得性感染有关的最普遍的真菌病原体之一。它与上皮细胞表面的聚糖结合并引发感染。这个过程可以被模拟细胞表面聚糖结构的合成碳水化合物阻断。在这里，我们报告了对一系列具有芳香族（苯、方酸酰胺）和双环脂肪族（降冰片烯）支架的二价糖苷的评估，后者是此类小分子抗粘附糖缀合物的第一个例子。半乳糖苷1和6建立在芳香核心之上，是白色念珠菌粘附最有效的抑制剂在 138 μM 的浓度下，分别置换高达 36% 和 48% 的已经附着在上皮细胞上的酵母。值得注意的是，顺式-内-降冰片烯21的性能与苯核心衍生物相当。构象分析揭示了化合物1和21倾向于采用折叠构象。这些结果突出了降冰片烯作为合成抗粘附化合物的新型脂肪族支架的潜力。
京公网安备 11010802027423号