Anti-viral Compounds

Our group has performed significant research on the biological activity and total synthesis of the Amaryllidacea alkaloids. As well as being potent cytotoxic agents with activity against numerous cancer cell lines, we have demonstrated applications for the Amaryllidacea alkaloids as anti-viral compounds.

For example, we have found that trans-dihydrolycoricidine potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection. As well, trans-dihydronarciclasine and narciclasine were discovered as the most potent anti-Zika compounds currently known, inhibiting the cytopathic effect of the virus by 90% at sub-micromolar concentrations.

Our group is actively pursuing alternative syntheses of various Amaryllidacea alkaloids to enable further study of their impressive anti-viral activies.

Relevant Articles

Amaryllidacea Alkaloids

Synthetic Approaches to the Naturally Occuring Anticancer Amaryllidaceae Alkaloids trans-dihydrolycoricidine and trans-dihydronarciclasine. C. Zepeda-Velázquez, J. McNulty*, Studies in Natural Products Chemistry, 53, in press (2017).

Total Synthesis of the Natural Product (+)-trans-Dihydronarciclasine via an Asymmetric Organocatalytic [3+3]-Cycloaddition discovery of its potent anti-Zika Virus (ZIKV) Activity. O. Revu, C. Zepeda-Velazquez, A. Nielsen, J. McNulty*, R. H. Yolken, L. Jones-Brando, ChemistrySelect, 1, 5895-5899 (2016).

iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore With Multiple Effects Against Herpesvirus Infections. J. McNulty*, L. D’Aiuto, Y. Zhi, L. McClain, C. Zepeda-Velázquez, S. Ler, H. A.. Jenkins, M. B.  Yee, P. Piazza, R. H. Yolken, P. R. Kinchington, V. L. Nimgaonkar*, ACS Med. Chem. Lett., 7, 46-50 (2016).

Enantioselective Organocatalytic Michael-aldol Sequence to the Anticancer Natural Product (+)-trans-dihydrolycoricidine. J. McNulty*, C. Zepeda-Velazquez, Angew. Chem. Int. Ed. 53, 8450-8454 (2014). See also:  Short Synthesis of a Wildflower Alkaloid, Chem. & Eng. News, July 7th, 2014, p. 28-29.  See also: Synfacts, 10, 982 (2014).