title: Digitoxin analogues with improved anticytomegalovirus activity.
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.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Hua-Yu L
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Venkatadri
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
authors.forename: De-Xue
authors.initials: DX
authors.lastname: Fu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland 21287, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Forman
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Sumit O
authors.initials: SO
authors.lastname: Bajaj
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: George A
authors.initials: GA
authors.lastname: O'Doherty
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
authors.forename: Ravit
authors.initials: R
authors.lastname: Arav-Boger
keywords: Cardiac glycosides; cytomegalovirus; digitoxin analogues; virus inhibition