Dipartimento di Farmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy.
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 3, 56124 Pisa, Italy.
Molecules. 2019 Sep 28;24(19):3520. doi: 10.3390/molecules24193520.
Conjugation of known biologically active molecules to carbohydrate frameworks represents a valuable option for the preparation of hybrid, structurally-related families of compounds with the aim of modulating their biological response. Therefore, we present here a study on the preparation of d-, d-, d-, and d- glycoconjugates of an established -hydroxyindole-based (NHI) inhibitor of lactated dehydrogenase (LDH). Structural variations involved the sugar stereochemistry and size as well as the anchoring point of the NHI on the carbohydrate frame (either C-1 or C-6). In the case of the galactose anomeric glycoconjugate (C-1), intriguing solvent-dependent effects were observed in the glycosylation stereochemical outcome. The biological activity of the deprotected glycoconjugates in contrasting lactate formation and cancer cell proliferation are described.
将已知具有生物活性的分子与碳水化合物框架结合，代表了一种制备具有混合结构、相关结构家族化合物的有价值的方法，旨在调节它们的生物反应。因此，我们在这里介绍了一种制备基于 d-、d-、d- 和 d- 糖的已建立的 -羟基吲哚（NHI）乳酸脱氢酶（LDH）抑制剂的研究。结构变化涉及糖的立体化学和大小以及 NHI 在碳水化合物框架上的连接点（C-1 或 C-6）。在半乳糖差向异构糖基化产物（C-1）的情况下，观察到有趣的溶剂依赖性影响糖基化立体化学结果。描述了去保护糖基化产物在对比乳酸形成和癌细胞增殖方面的生物活性。
