Identification and Synthesis of Quinolizidines with Anti-Influenza A Virus Activity
Identification and Synthesis of Quinolizidines with Anti-Influenza A Virus Activity
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DOI：
10.1021/ml500236n
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发表时间：
2014-08-01
影响因子：
4.2
通讯作者：
Chen, Chin-Ho
中科院分区：
文献类型：
--
作者：
Dang, Zhao;Jung, Katherine;Chen, Chin-Ho
甲型流感病毒感染会引起一种传染性呼吸道疾病，对人类健康构成威胁。然而，可用的抗甲型流感治疗剂有限，耐药病毒的出现进一步加剧了这种情况。苦参喹里西啶生物碱是一种新的抗甲型流感病毒药物。在所测试的槐属生物碱中，二氢苦豆碱表现出最强的活性，其EC 50为11.2 μ M。喹里西啶生物碱的效力通过对苦豆碱分子进行化学修饰而提高约5倍。这些化合物对H1N1甲型流感病毒有效，该病毒对两种抗流感药物奥司他韦和金刚烷胺具有耐药性。喹里西啶生物碱作为有效的新型抗甲型流感药物的鉴定可能有助于开发新的治疗方法。
Influenza A virus infection causes a contagious respiratory illness that poses a threat to human health. However, there are limited anti-influenza A therapeutics available, which is further compounded by the emergence of drug resistant viruses. In this study, Sophora quinolizidine alkaloids were identified as a new class of anti-influenza A virus agents. Among the tested Sophora alkaloids, dihydroaloperine exhibited the most potent activity with an EC50 of 11.2 mu M. The potency of the quinolizidine alkaloids was improved by approximately 5-fold with chemical modifications on the aloperine molecule. These compounds were effective against an H1N1 influenza A virus that was resistant to the two antiflu drugs oseltamivir and amantadine. The identification of the quinolizidine alkaloids as effective and novel anti-influenza A agents may aid in the development of new therapeutics.