iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections
详细信息 查看全文
- 作者：James McNulty ; Leonardo D’Aiuto ; Yun Zhi ; Lora McClain ; Carlos Zepeda-Velázquez ; Spencer Ler ; Hilary A. Jenkins ; Michael B. Yee ; Paolo Piazza ; Robert H. Yolken ; Paul R. Kinchington ; Vishwajit L. Nimgaonkar
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2016
- 出版时间：January 14, 2016
- 年：2016
- 卷：7
- 期：1
- 页码：46-50
- 全文大小：319K
- ISSN：1948-5875
文摘
The Amaryllidaceae alkaloid trans-dihydrolycoricidine 7 and three analogues 8–10 were produced via asymmetric chemical synthesis. Alkaloid 7 proved superior to acyclovir, the current standard for herpes simplex virus, type 1 (HSV-1) infection. Compound 7 potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection. A configurationally defined (3R)-secondary alcohol at C3 proved crucial for efficacious inhibition of lytic HSV-1 infection.