诱导多能干细胞神经元检测鉴定出对疱疹病毒感染具有多种作用的石蒜科药效基团。
iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections.
作者信息
McNulty James, D'Aiuto Leonardo, Zhi Yun, McClain Lora, Zepeda-Velázquez Carlos, Ler Spencer, Jenkins Hilary A, Yee Michael B, Piazza Paolo, Yolken Robert H, Kinchington Paul R, Nimgaonkar Vishwajit L
机构信息
Department of Chemistry and Chemical-Biology, McMaster University , 1280 Main Street, West Hamilton, Ontario L8S 4M1, Canada.
Department of Psychiatry, University of Pittsburgh, School of Medicine , 3811 O'Hara Street, Pittsburgh, Pennsylvania 15213, United States.
出版信息
ACS Med Chem Lett. 2015 Nov 19;7(1):46-50. doi: 10.1021/acsmedchemlett.5b00318. eCollection 2016 Jan 14.
Abstract
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.
摘要
石蒜科生物碱反式二氢石蒜碱7及其三种类似物8 - 10通过不对称化学合成制备。生物碱7被证明优于阿昔洛韦，阿昔洛韦是目前治疗1型单纯疱疹病毒（HSV - 1）感染的标准药物。化合物7能有效抑制HSV - 1的裂解感染，显著降低HSV - 1的再激活，并更有效地抑制水痘带状疱疹病毒（VZV）的裂解感染。结果证明，C3位具有构型明确的(3R)-仲醇对于有效抑制HSV - 1裂解感染至关重要。
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