Digitoxin analogues with improved anticytomegalovirus activity

ACS Med Chem Lett. 2014 Jan 25;5(4):395-9. doi: 10.1021/ml400529q.

Hongyi Cai ¹, Hua-Yu L Wang ², Rajkumar Venkatadri ¹, De-Xue Fu ¹, Michael Forman ³, Sumit O Bajaj ², Hongyan Li ², George A O'Doherty ², Ravit Arav-Boger ¹

Affiliations

1 Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
2 Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
3 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.

PMID: 24900847 DOI: 10.1021/ml400529q

Abstract

Cardiac glycosides are potent inhibitors of Cancer cell growth and possess Antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We show that sugar type and sugar length attached to the steroid core structure affects its anticytomegalovirus activity. Structure-activity relationship (SAR) studies identified the l-sugar containing cardiac glycosides as having improved anti-CMV activity and may lead to better understanding of how these compounds inhibit CMV replication.

Keywords

Cardiac glycosides; cytomegalovirus; digitoxin analogues; virus inhibition.

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