title: Artemisinin-derived dimer phosphate esters as potent anti-cytomegalovirus (anti-CMV) and anti-cancer agents: a structure-activity study.
abstract: We recently reported the anti-cancer and anti-cytomegalovirus (CMV) activity of artemisinin-derived trioxane diphenylphosphate dimer 838. To probe the relationship between chemical structure and anti-CMV and anti-cancer activities, we now report synthesis and evaluation of a series of eight new dimer phosphate ester analogs of 838. This series of novel molecules was screened against human foreskin fibroblasts (HFFs) infected with CMV and against the human Jurkat T cell acute lymphoblastic leukemia cell line. This SAR study confirms the very high anti-CMV and anti-cancer potencies of dimer diphenyl phosphate ester 838 without its being toxic to normal cells.
authors.affiliation: Department of Chemistry, School of Arts and Sciences, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Mott
authors.forename: Ran
authors.initials: R
authors.lastname: He
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chen
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Fox
authors.forename: Curt I
authors.initials: CI
authors.lastname: Civin
authors.forename: Ravit
authors.initials: R
authors.lastname: Arav-Boger
authors.forename: Gary H
authors.initials: GH
authors.lastname: Posner
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D019281:Dimerization; D004952:Esters; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy*; D010710:Phosphates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D037621:Artemisinins; D004952:Esters; D010710:Phosphates; C031327:artemisinin