抗流感藥物之合成與活性研究:瑞樂沙 (Relenza®) 衍生物

Abstract

摘要 流感病毒現今仍為高發病與高致死疾病，普遍造成人類健康的問題。最近H5N1禽流感藉由遷徙的鳥類感染，疫情遍及中國、非洲和歐洲。而動物間所感染的禽流感病毒皆是由水生鳥類提供感染源。 Zanamivir可以有效抑制流感病毒的神經胺酸酵素，使神經胺酸酵素無法有效的切除與宿主細胞連接的未端Sialic acid。由於流感病毒無法擴散感染其它宿主細胞，可達到對抗流感病毒的效果。

根據文獻報導，在zanamivir藥物七號碳上的羥基，並不會影響藥物對流感病毒的結合效果。因此可以修飾七號碳上的基團，與磁性奈米粒子結合，由於多重價效應可提升與流感病毒結合的能力。

將zanamivir藥物與磁奈米粒子結合有一些優點。除了多重價效應可提升抑制效果外，還可容易分離流感病毒與易控制藥物到達受感染的細胞，以集中藥效。 另一方面，zanamivir在七號碳也可結合caffeic acid。Caffeic acid是phenolic acid的成員之一，主要有抗氧化、抗發炎的活性。所以接上caffeic acid的zanamivir衍生物可以增加藥物的功能性，以達到有效對抗流感病毒。

Abstract Influenza virus is still a major worldwide health problem today that causes substantial morbidity and mortality. Recently, the H5N1 subtype of avian influenza virus has spread over China, Africa, and European union mainly by migratory birds. Wild waterfowls are the major reservoir of influenza viruses, and all influenza viruses in other animal species are thought to be derived from these birds.

The zanamivir is one of the most potent inhibitors of influenza neuraminidase (NA), which is believed to catalyze the cleavage of terminal sialic acid residues. The zanamivir at C7 position does not influence the recognition with influenza virus, thus it can be modified to combine with nanoparticle to enhance the binding affinity presumably via multivalent effect. The zanamivir linked magnetic nanoparticle has the advantageous features of multivalency effect, easy isolation of influenza virus for assay, and well control to reach the target cell of infection.

On the other hand, the zanamivir at C7 position can be modified to couple caffeic acid. Caffeic acid, a phenolic acid present in many dietary plants has been shown to confer antioxidant and anti-inflammatory activities. So it may make the drug more functional against influenza virus.