A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells

文献类型： 外文期刊

第一作者： Zhou, Cui

作者： Zhou, Cui;Ye, Wenchong;Wang, Meizhu;Liao, Guohao;Huang, Weiping;Zhou, Cui;Ye, Wenchong;Wang, Meizhu;Qi, Dongxia;Wang, Xiaoyang;Zhou, Wen;Cao, Yongjun;Li, Houkai;Chen, Wenming;Chen, Wenming;Wang, Xiaoyang;Zhou, Wen

作者机构：

关键词： BLM disaccharide; Gulose; SAR; Selective uptake mechanism; Imaging study

期刊名称：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY （ 影响因子：7.088； 五年影响因子：6.427 ）

ISSN： 0223-5234

年卷期： 2021 年 226 卷

页码：

收录情况： SCI

摘要： Eight mono- or disaccharide analogues derived from BLM disaccharide, along with the corresponding carbohydate-dye conjugates have been designed and synthesized in this study, aiming at exploring the effect of a gulose residue on the cellular binding/uptake of BLM disaccharide and it possible uptake mechanism. Our evidence is presented indicating that, for the cellular binding/uptake of BLM disaccharide, a gulose residue is an essential subunit but unrelated to its chemical nature. Interestingly, D-gulose-dye conjugate is able to selectively target A549 cancer cells, but L-gulose-dye conjugate fails. Further uptake mechanism studies demonstrate D-gulose-dye derivatives similar to BLM disaccharide-dye ones behave in a temperature- and ATP-dependent manner, and are partly directed by the GLUT1 receptor. Moreover, D-gulose modifying gemcitabine 53a exhibits more potent antitumor activity compared to derivatives 53b-c in which gemcitabine is decorated with other monosaccharides. Taken together, the monosacharide D-gulose conjugate offers a new strategy for solving cytotoxic drugs via the increased tumor targeting in the therapy of lung cancer. (C) 2021 Elsevier Masson SAS. All rights reserved.

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