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

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...

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Veröffentlicht in:European journal of medicinal chemistry 2021-12, Vol.226, p.113866-113866, Article 113866
Hauptverfasser: Zhou, Cui, Ye, Wenchong, Cao, Yongjun, Wang, Meizhu, Qi, Dongxia, Liao, Guohao, Li, Houkai, Huang, Weiping, Chen, Wenming, Wang, Xiaoyang, Zhou, Wen
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Design and synthesis of eight mono- and disaccharide-dye conjugates.•A gulose reside is an essential group for the cellular uptake of BLM disaccharide.•Fluorescence intensity of d-gulose-dye conjugates is similar to that of natural BLM disaccharide.•Uptake mechanism of d-gulose is in a temperature- and ATP-dependent manner.•d-Gulose modifying gemcitabine favors its selective targeting to A549 cancer cells.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2021.113866