糖基腙衍生物的設計與合成作為抗登革熱病毒劑

Design and synthesis of glycosyl hydrazone derivatives as anti-dengue virus agent

郭建程(Chain-Cheng Kuo)

指導教授 ： 曾志華

高雄醫學大學/藥學院/藥學系碩士班/碩士(2018年)

摘要

根據文獻可以發現，腙對於抗病毒、抗細菌、抗驚厥、止痛、抗發炎有著不錯的生物活性。在我們實驗室以前的研究中，合成了一系列N-酰基腙化合物，並評估其抗登革熱病毒活性。雖然它們表現出潛在的抗登革熱病毒活性，但主要的缺點是它們的水溶性不甚理想。我們的研究的目的是將糖基團引入我們以前的N-酰基腙骨架，以提高水溶性，同時保持或調節其抗登革熱病毒活性。合成一系列糖基N-酰基腙衍生物，並評價其抗登革熱病毒活性。我們發現，相較於Ribavirin，化合物36和64對於DENV2有更好的抑制性，且化合物36和64細胞毒性已經消失，因此比起Ribavirin化合物36和64有著較好的選擇性。

關鍵字

登革熱 ； 水溶解度 ； 腙糖

並列摘要

Hydrazones have been demonstrated to possess various bioactivities such as antimicrobial, anticonvulsant, analgesic, anti-inflammatory, antiplatelet, and antitumoral activities. In our previous study, a series of N-acylhydrazone compounds were synthesized and evaluated for their anti-dengue virus activity. Although they exhibited potential anti-dengue virus activity, the main drawback is their poor water solubility. Our aim of this study is to introduce the sugar moiety to our previous acylhydrazone skeleton to improve water solubility while keeping or modulating their anti-dengue virus activities. A number of glycosyl acylhydrazone derivatives was synthesized and evaluated for their anti-Dengue virus activity. Both 64 and 36 were found to be more potent than ribavirin in the inhibition of DENV2 RNA expression in Huh-7-DV-Fluc cells and the inhibition is in a dose-dependent manner. Compounds 64 and 36 reduced DENV replication in both viral protein and mRNA levels, and no significant cell cytotoxicity was detected, with greater than 50% viability of Huh-7-DV-Fluc cells at a concentration of 200 μM.

並列關鍵字

anti-dengue virus ； water solution ； sugar

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