Design, synthesis and biological evaluation of enzymatically cleavable NSAIDs prodrugs derived from self-immolative dendritic scaffolds for the treatment of inflammatory diseases.
Design, synthesis and biological evaluation of enzymatically cleavable NSAIDs prodrugs derived from self-immolative dendritic scaffolds for the treatment of inflammatory diseases.
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用于治疗炎症疾病的自焚树突支架衍生的可酶促裂解的 NSAID 前药的设计、合成和生物学评价。
DOI：
10.1016/j.bmc.2013.05.006
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发表时间：
2013
影响因子：
3.5
通讯作者：
Ouyang Liang
中科院分区：
文献类型：
--
作者：
Jinbao Wei;Jianyou Shi;Jing Zhang;Gu He;Junzhu Pan;J. He;Rui Zhou;Li Guo;Ouyang Liang
非甾体抗炎药（NSAIDs）的树枝状前体药物给药系统改善了药物分子的性质，降低了对胃粘膜的刺激性和副作用。为了寻找一种更有效的方法在非甾体抗炎药的树枝状前药，本文中，三个不同的树枝状支架酶裂解的napolipen共轭物已合成在收敛的方法和NMR和MS技术进行了表征。这些自分解的树突状NISADs前药在单个酶促活化步骤后被编程释放多个有效的萘普生分子，并且在50%的人血浆中，在体外测定24小时后，从化合物T3释放的药物达到47.3%。此外，还发现所有前药都保持更显著的抗炎活性，对HEK293细胞没有显著的细胞毒性，并且与其单体对应物萘普生相比，体内致溃疡潜力程度更低。这些结果为开发新的树枝状NSAID前药提供了有效的途径。
It has been reported that delivery systems based on dendritic prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) improved the properties of drug molecules and reduced the side effects and irritation on the gastric mucosa. To find a more effective way in NSAIDs dendritic prodrugs, in this paper, three different dendritic scaffolds of enzymatically cleavable naproxen conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. These self-immolative dendritic NISADs prodrugs programmed to release multiple molecules of the potent naproxen after a single enzymatic activation step, and in 50% human plasma, the drug released from the compound T3 reaching 47.3% after 24h in vitro assay. Moreover, all prodrugs were also found to maintain more significant anti-inflammatory activity, no significant cytotoxicity against HEK293 cells and less degree of ulcerogenic potential in vivo than their monomeric counterpart naproxen. These results provided an effective entry to the development of new dendritic NSAIDs prodrugs.
影响因子：
4.9
作者：
Ren K;Purdue PE;Burton L;Quan LD;Fehringer EV;Thiele GM;Goldring SR;Wang D
通讯作者：
Wang D