Structure-activity relationship of propylene glycol alginate sodium sulfate derivatives for blockade of selectins binding to tumor cells
Structure-activity relationship of propylene glycol alginate sodium sulfate derivatives for blockade of selectins binding to tumor cells
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海藻酸丙二醇酯硫酸钠衍生物阻断选择素与肿瘤细胞结合的构效关系
DOI：
10.1016/j.carbpol.2019.01.024
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发表时间：
2019
影响因子：
11.2
通讯作者：
Li Chunxia
中科院分区：
文献类型：
--
作者：
Ma He;Qiu Peiju;Xin Meng;Xu Ximing;Wang Zhuoya;Xu Huixin;Yu Rilei;Xu Xiaoxiao;Zhao Chenyang;Wang Xin;Guan Huashi;Yang Jinbo;Li Chunxia
选择素在转移小生境的形成中起主导作用，被认为是探索抗转移药物的重要靶点。在这项研究中，我们评估了海洋药物藻酸丙二醇酯硫酸钠（PSS）和一系列PSS衍生物对P-，L-或E-选择素介导的与肿瘤细胞结合的影响。我们发现PSS有效地阻止了P-或L-选择素与肿瘤细胞的结合。构效关系研究表明，PSS的活性与其C-2/C-3位的硫酸酯基、C-6位的丙二醇取代基、古罗糖醛酸与甘露糖醛酸的比例以及分子量有关。此外，PSS衍生物在体内对肺转移有明显的抑制作用，表明PSS及其衍生物是一种潜在的抗肺转移药物。
Selectins dominate the formation of the metastasis niche and are considered important targets for exploring antimetastatic drugs. In this study, we evaluated the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) and a series of PSS derivatives on P-, L- or E-selectin-mediated binding with tumor cells. We found that PSS effectively prevented the binding of P- or L-selectin with tumor cells. Moreover, the structure-activity relationship study indicated that the activity of PSS is related to the sulfate group at the C-2/C-3 position, the propylene glycol substituent at the C-6 position, the ratio of guluronic acid to mannuronic acid, and the molecular weight. Additionally, PSS derivatives significantly suppressed lung metastasisin vivo.Our results demonstrated that PSS and its derivatives are potential antimetastatic drugs candidates.