Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation
Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation
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寡糖-喜树碱缀合物作为潜在的抗肿瘤药物：设计、合成和生物学评价
DOI：
10.1016/j.ejmech.2020.112509
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发表时间：
2020-09-15
影响因子：
6.7
通讯作者：
Zhou, Wen
中科院分区：
文献类型：
--
作者：
Li, Maolin;Ye, Wenchong;Zhou, Wen
合成了30种新型20（S）-O-连接喜树碱（CPT）糖缀合物。它们显示出比伊立替康更强的体外细胞毒性，但在100.0 μ M时观察到非常弱的直接拓扑异构酶I（Topo I）抑制。寡聚糖的种类、PEG连接基的长度和乙酰基对新合成的CPT糖缀合物的细胞毒性、选择性、水溶性和稳定性有明显的影响。与CPT相比，在引入的酯部分中具有与二甘醇连接的博来霉素（BLM）二糖的构建体40表现出上级抗肿瘤活性和明显的选择性。在动物急性毒性静脉注射（160 mg/kg）中未检测到毒性。总的来说，具有肿瘤靶向的寡糖与CPT的20（S）-OH的连接可以为当前Topo I毒物引起的令人生畏的问题提供解决方案。(C)2020 Elsevier Masson SAS。All rights reserved.
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. (C) 2020 Elsevier Masson SAS. All rights reserved.