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首页> 外文期刊>RSC Advances >Synthesis of tricyclic carbohydrate–benzene hybrids as selective inhibitors of galectin-1 and galectin-8 N-terminal domains
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Synthesis of tricyclic carbohydrate–benzene hybrids as selective inhibitors of galectin-1 and galectin-8 N-terminal domains

机译：三环碳水化合物 - 苯杂交种作为半抗凝蛋白-1和半抗凝蛋白-8 n末端结构域的选择性抑制剂

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As the galactoside binding family of galectin proteins is involved in many physiological and pathological processes, the inhibitors of these proteins are considered to be of significant interest in the treatment of diseases such as cancer and fibrosis. Herein, fused tricyclic carbohydrate–benzene hybrid core structures are reported to be the selective inhibitors of galectin-1 and the N-terminal domain of galectin-8 by a competitive fluorescence polarization assay. The key intermediates mono- or diiodo tricyclic carbohydrate–benzene hybrids were synthesized from protected 2-bromo-3- O -propargyl- D -galactose via a domino reaction and subsequently utilized for further derivatization by Stille couplings to achieve derivatives carrying substituents at C10 and/or C11. Several compounds showed affinity for the galectin-1 and galectin-8 N-terminal (8N) domains; however, weak or even no binding was observed for galectin-3. Monosubstituted derivatives at C10 or C11 exhibited better affinity for galectin-8N than di-substituted derivatives at C10 or C11. Especially, a benzyl substituent or p -fluorobenzyl substituent at C11 displayed affinity and selectivity for galectin-1 and galectin-8N over galectin-3. This suggests that tricyclic carbohydrate–benzene hybrids are promising scaffolds for the development of selective galectin-1 and galectin-8N inhibitors.
机译：随着半乳糖蛋白蛋白的半乳糖苷结合家族涉及许多生理和病理过程，这些蛋白质的抑制剂被认为对治疗癌症和纤维化等疾病的患者具有重要兴趣。这里，据报道，融合的三环碳水化合物 - 苯杂化核心结构是通过竞争性荧光偏振测定的半抗凝蛋白-1和半抗凝蛋白-8的N-末端结构域的选择性抑制剂。通过多米诺反应从受保护的2-溴-3-O-丙基-GAlactose合成单碘代或二极管三环碳水化合物 - 苯杂交杂交物，随后通过STILLE联轴器进一步用于进一步衍生化，以实现C10的衍生物载体载体的衍生物/或c11。几种化合物对Galectin-1和Galectin-8 N-末端（8N）结构域具有亲和力;然而，对于Galectin-3，观察到弱甚至没有结合。 C10或C11的单取出的衍生物对G10或C11的二取代衍生物具有更好的亲眼性亲和力。特别是，C11的苄基取代基或氟苄苄基取代基在G11和Galectin-3上显示了Galectin-1和Galectin-8N的亲和力和选择性。这表明三环碳水化合物 - 苯杂交物是有前途的支架，用于开发选择性Galectin-1和Galectin-8N抑制剂。

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