2. Academic Validation
  3. A gulose moiety contributes to the belomycin (BLM) disaccharide selective targeting to lung cancer cells

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

  • Eur J Med Chem. 2021 Dec 15:226:113866. doi: 10.1016/j.ejmech.2021.113866.
Cui Zhou 1,  Wenchong Ye 1,  Yongjun Cao 2,  Meizhu Wang 1,  Dongxia Qi 3,  Guohao Liao 4,  Houkai Li 5,  Weiping Huang 4,  Wenming Chen 6,  Xiaoyang Wang 7,  Wen Zhou 8
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, China; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China.
  • 2 Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, 510120, Guangdong, China.
  • 3 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China.
  • 4 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, China.
  • 5 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 6 Department of Pharmaceutical Production Center＆TCM and Ethnomedicine Development International Laboratory, The First Hospital of Hunan University of Chinese Medicine, 95, Shaoshan Rd, Changsha, Hunan, 41007, China. Electronic address: haoming0007@163.com.
  • 7 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China; Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China. Electronic address: wxy@shvri.ac.cn.
  • 8 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China; Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China. Electronic address: zhouwen60@126.com.
PMID: 34619466 DOI: 10.1016/j.ejmech.2021.113866
Abstract

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.

Keywords

BLM disaccharide; Gulose; Imaging study; SAR; Selective uptake mechanism.

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