摘要
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 mu M. 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 glyco-conjugates. 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.
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单位思茅师范高等专科学校; 1; 广州中医药大学; 湖南中医药大学; 中山大学; 复旦大学