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应用一种三脚架型六脲受体与抗肿瘤药物磷酸考布他汀A4结合。

Applying a Tripodal Hexaurea Receptor for Binding to an Antitumor Drug, Combretastatin-A4 Phosphate.

作者信息

Kong Yu, Zhang Rong, Li Boyang, Zhao Wei, Wang Ji, Sun Xiao-Wen, Lv Huihui, Liu Rui, Tang Juan, Wu Biao

机构信息

Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China.

College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.

出版信息

Materials (Basel). 2024 May 27;17(11):2570. doi: 10.3390/ma17112570.

Abstract

Phosphates play a crucial role in drug design, but their negative charge and high polarity make the transmembrane transport of phosphate species challenging. This leads to poor bioavailability of phosphate drugs. Combretastatin-A4 phosphate (CA4P) is such an anticancer monoester phosphate compound, but its absorption and clinical applicability are greatly limited. Therefore, developing carrier systems to effectively deliver phosphate drugs like CA4P is essential. Anion receptors have been found to facilitate the transmembrane transport of anions through hydrogen bonding. In this study, we developed a tripodal hexaurea anion receptor () capable of binding anionic CA4P through hydrogen bonding, with a binding constant larger than 10 M in a DMSO/water mixed solvent. demonstrated superior binding ability compared to other common anions, and exhibited negligible cell cytotoxicity, making it a promising candidate for future use as a carrier for drug delivery.

摘要

磷酸盐在药物设计中起着至关重要的作用,但其负电荷和高极性使得磷酸盐类物质的跨膜运输具有挑战性。这导致磷酸盐药物的生物利用度较差。磷酸柯里拉京(CA4P)就是这样一种抗癌单酯磷酸盐化合物,但其吸收和临床适用性受到极大限制。因此,开发载体系统以有效递送像CA4P这样的磷酸盐药物至关重要。已发现阴离子受体可通过氢键促进阴离子的跨膜运输。在本研究中,我们开发了一种三脚架型六脲阴离子受体(),它能够通过氢键与阴离子型CA4P结合,在二甲基亚砜/水混合溶剂中的结合常数大于10 M。与其他常见阴离子相比,表现出卓越的结合能力,并且细胞毒性可忽略不计,这使其成为未来用作药物递送载体的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1bc/11173554/346e4f8518b3/materials-17-02570-g001.jpg

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