Nitric Oxide-Releasing Cyclodextrins,Journal of the American Chemical Society

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Nitric Oxide-Releasing Cyclodextrins
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2018-09-20 , DOI: 10.1021/jacs.8b07661
Haibao Jin ₁ , Lei Yang ₁ , Mona Jasmine R Ahonen ₁ , Mark H Schoenfisch ₁

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A series of secondary amine-modified cyclodextrin (CD) derivatives was synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl, methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas under alkaline conditions yielded N-diazeniumdiolate-modified CD derivatives. Adjustable NO payloads (0.6-2.4 μmol/mg) and release half-lives (0.7-4.2 h) were achieved by regulating both the amount of secondary amine precursors and the functional groups around the NO donors. The bactericidal action of these NO-releasing cyclodextrin derivatives was evaluated against Pseudomonas aeruginosa, a Gram-negative pathogen, with antibacterial activity proving dependent on both the NO payload and exterior modification. Materials containing a high density of NO donors or primary amines exhibited the greatest ability to eradicate P. aeruginosa. Of the materials prepared, only the primary amine-terminated heptasubstituted CD derivatives exhibited toxicity against mammalian L929 mouse fibroblast cells. The NO donor-modified CD was also capable of delivering promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug-releasing therapeutic.

中文翻译：

释放一氧化氮的环糊精

合成了一系列具有不同外部端基（即羟基、甲基、甲氧基和伯胺）的仲胺修饰的环糊精（CD）衍生物。随后在碱性条件下与一氧化氮 (NO) 反应生成 N-二醇二氮烯鎓修饰的环糊精衍生物。通过调节仲胺前体的量和 NO 供体周围的官能团，可以实现可调节的 NO 有效负载（0.6-2.4 μmol/mg）和释放半衰期（0.7-4.2 h）。这些释放 NO 的环糊精衍生物对铜绿假单胞菌（一种革兰氏阴性病原体）的杀菌作用进行了评估，抗菌活性被证明依赖于 NO 有效负载和外部修饰。含有高密度NO供体或伯胺的材料表现出最大的根除铜绿假单胞菌的能力。在所制备的材料中，只有伯胺封端的七取代CD衍生物表现出针对哺乳动物L929小鼠成纤维细胞的毒性。NO供体修饰的CD还能够递送异丙嗪（一种疏水性药物），从而显示出作为双药物释放治疗剂的潜力。

更新日期：2018-09-20

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