title: Efficacy of methylenecyclopropane analogs of nucleosides against herpesvirus replication in vitro.
abstract: We have reported previously that purine methylenecyclopropane analogs are potent agents against cytomegaloviruses. In an attempt to extend the activity of these compounds, the 2-amino-6-cyclopropylaminopurine analog, QYL-1064, was selected for further study by modifying the purine 6 substituent. A total of 22 analogs were tested against herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), human cytomegalovirus (HCMV), murine cytomegalovirus (MCMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV-6) and human herpesvirus type 8 (HHV-8). Ten of the analogs had activity against at least one of the viruses tested. One compound had moderate activity against HSV-1 and six had activity against VZV. All but one compound was active against HCMV with a mean EC50 of 2.1 +/- 0.6 microM, compared with a mean EC50 of 3.9 +/- 0.8 microM for ganciclovir. Of special interest was the fact that eight of the ten compounds were active against both HHV-6A and HHV-6B with mean EC50 values of 6.0 +/- 5.2 mciroM and <2.4 +/- 1.5 microM, respectively. Only two compounds had activity against EBV, whereas all but one compound was active against HHV-8 with a mean EC50 of 3.1 +/- 1.7 microM. These results indicate that members of this series of methylenecyclopropane analogs are highly active against HCMV, HHV-6, and HHV-8 but are less active against HSV, VZV, and EBV.
authors.affiliation: The University of Alabama School of Medicine, Birmingham, Alabama, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kushner
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Williams
authors.forename: Caroll B
authors.initials: CB
authors.lastname: Hartline
authors.forename: Emma A
authors.initials: EA
authors.lastname: Harden
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Bidanset
authors.forename: Xinchao
authors.initials: X
authors.lastname: Chen
authors.forename: Jiri
authors.initials: J
authors.lastname: Zemlicka
authors.forename: Earl R
authors.initials: ER
authors.lastname: Kern
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000737:chemistry; D003587:Cytomegalovirus / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D006151:Guanosine / Q000031:analogs & derivatives*; D006564:Herpesviridae / Q000187:drug effects*; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects; D015654:Herpesvirus 6, Human / Q000187:drug effects; D019288:Herpesvirus 8, Human / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D018146:Muromegalovirus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D006151:Guanosine; D000241:Adenosine