IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections

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

doi:10.1021/acsmedchemlett.5b00318

IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English (US)
Pages (from-to)	46-50
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	7
Issue number	1
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00318
State	Published - Jan 14 2016

Keywords

Amaryllidaceae
HSV-1
Herpesvirus
alkaloid
stem cells
varicella zoster

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.5b00318

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McNulty, J., D'Aiuto, L., Zhi, Y., McClain, L., Zepeda-Velázquez, C., Ler, S., Jenkins, H. A., Yee, M. B., Piazza, P., Yolken, R. H., Kinchington, P. R., & Nimgaonkar, V. L. (2016). IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections. ACS Medicinal Chemistry Letters, 7(1), 46-50. https://doi.org/10.1021/acsmedchemlett.5b00318

McNulty, J, D'Aiuto, L, Zhi, Y, McClain, L, Zepeda-Velázquez, C, Ler, S, Jenkins, HA, Yee, MB, Piazza, P, Yolken, RH, Kinchington, PR & Nimgaonkar, VL 2016, 'IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections', ACS Medicinal Chemistry Letters, vol. 7, no. 1, pp. 46-50. https://doi.org/10.1021/acsmedchemlett.5b00318

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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.",

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AU - Zepeda-Velázquez, Carlos

AU - Ler, Spencer

AU - Jenkins, Hilary A.

AU - Yee, Michael B.

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IPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections

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Keywords

ASJC Scopus subject areas

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