Selective bone targeting 5-fluorouracil prodrugs: Synthesis and preliminary biological evaluation
Selective bone targeting 5-fluorouracil prodrugs: Synthesis and preliminary biological evaluation
复制标题
选择性骨靶向5-氟尿嘧啶前药：合成和初步生物学评价
DOI：
10.1016/j.bmc.2011.05.004
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发表时间：
2011-06-15
影响因子：
3.5
通讯作者：
Guo, Li
中科院分区：
文献类型：
--
作者：
Ouyang, Liang;He, Dongsheng;Guo, Li
众所周知，骨肿瘤是一种难以治疗的疾病，需要频繁且大剂量的全身化疗。在全身给药后将抗癌药物靶向至骨可以提供更大的治疗功效和更低的给药频率。本文采用聚合法合成了一系列骨靶向的天冬氨酸寡肽5-氟尿嘧啶偶联物，并通过核磁共振和质谱技术对其结构进行了表征。在体外条件下，它们的羟基磷灰石（HAP）的亲和力，药物释放和细胞毒性特性进行了评价。所有的前药都是水溶性的，并且对HAP表现出高亲和力。通过在生理条件下切割不同的键而发生的活性药物部分的有效释放显著减少了活的人癌细胞的数量。从体内分布来看，这些化合物具有骨选择性高、半衰期长的特点。这些结果为开发新的骨靶向化疗药物提供了有效的途径。(C)2011爱思唯尔有限公司版权所有。
Bone tumor is a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered chemotherapy. Targeting anticancer drug to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. In this paper, a series of bone targeting Asp oligopeptides 5-fluorouracil conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their hydroxyapatite (HAP) affinity, drug release and cytotoxicity characteristics were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP. The efficient release of the active drug moiety occurring by the cleavage of different linkage in physiological conditions significantly reduced the number of viable human cancer cells. From in vivo distribution, we get these compounds with high bone-selectivity and long halflife. These results provided an effective entry to the development of new bone targeting chemotherapeutic drugs. (C) 2011 Elsevier Ltd. All rights reserved.