2. Academic Validation
  3. Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation

Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation

  • Eur J Med Chem. 2020 Sep 15;202:112509. doi: 10.1016/j.ejmech.2020.112509.
Maolin Li 1,  Wenchong Ye 1,  Kaishuo Fu 1,  Cui Zhou 1,  Yonghui Shi 2,  Weiping Huang 1,  Wenming Chen 3,  Jiliang Hu 1,  Zhilin Jiang 4,  Wen Zhou 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, E. 232, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, China.
  • 2 Department of Pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China.
  • 3 Department of Pharmaceutical Production Center, The First Affiliated Hospital of Hunan University of Chinese Medicine, 95, Shaoshan Rd, Changsha, Hunan, 41007, China.
  • 4 Puer University, Puer, 665000, Yunan, China; Institutes of Integrative Medicine, Fudan University, Shanghai, 200040, China. Electronic address: zhilin_jiang@126.com.
  • 5 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, E. 232, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, China. Electronic address: zhouwen60@126.com.
PMID: 32668379 DOI: 10.1016/j.ejmech.2020.112509
Abstract

Thirty novel 20 (S)-O-linked camptothecin (CPT) glycoconjugates were synthesized. They showed more potent in vitro cytotoxicities over irinotecan, but very weak direct Topoisomerase I (Topo I) inhibition was observed at 100.0 μM. Oligosaccharide types, length of a PEG linker and acetyl groups exerted obvious effects on cytotoxicity, selectivity, water solubility and stability of the newly synthesized CPT glycoconjugates. Construct 40, with a bleomycin (BLM) disaccharide linked to diethylene glycol in the introduced ester moiety, demonstrated a superior antitumor activity and a distinct selectivity compared to CPT. No toxicity was detectable in animal acute toxicity intravenously (160 mg/kg). Collectively, attachment of oligosaccharides with tumor targeting to 20 (S)-OH of CPT could offer a solution to the daunting problems posed by current Topo I poisons.

Keywords

Anti-tumor activity; Aqueous solubility and stability; Camptothecin; Oligosaccharides; Toxicological assessment.

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