artemisinin-derived dimers have greatly improved anti-cytomegalovirus activity compared to artemisinin monomersartemisinin-derived二聚体anti-cytomegalovirus活动与青蒿素单体相比有了很大的提高.pdfVIP

Artemisinin-Derived Dimers Have Greatly Improved Anti-Cytomegalovirus Activity Compared to Artemisinin Monomers 1 1 2 2 3 3 Ravit Arav-Boger *, Ran He , Chuang-Jiun Chiou , Jianyong Liu , Lauren Woodard , Andrew Rosenthal , 1 4 3 Lorraine Jones-Brando , Michael Forman , Gary Posner 1 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 3 Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, Maryland, United States of America, 4 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America Abstract Background: Artesunate, an artemisinin-derived monomer, was reported to inhibit Cytomegalovirus (CMV) replication. We aimed to compare the in-vitro anti-CMV activity of several artemisinin-derived monomers and newly synthesized artemisinin dimers. Methods: Four artemisinin monomers and two novel artemisinin-derived dimers were tested for anti-CMV activity in human fibroblasts infected with luciferase-tagged highly–passaged laboratory adapted strain (Towne), and a clinical CMV isolate. Compounds were evaluated for CMV inhibition and cytotoxicity. Results: Artemisinin dimers effectively inhibited CMV replication in human foreskin fibroblasts and human embryonic lung fibroblasts (EC50 for dimer sulfone carbamate and dimer primary alcohol 0.06 60.00 mM and 0.1560.02 mM respectively, in human foreskin fibroblasts) with no cytotxicity at concentrations required for complete CMV inhibition. Al