Anti-human cytomegalovirus activity and toxicity of sulfonated anthraquinones and anthraquinone derivatives.
Sulfonated anthraquinones and other anthraquinone derivatives were evaluated for anti-human cytomegalovirus (HCMV) activity, cytotoxicity and genotoxicity. Acid blues 40 and 129, acid black 48, alizarin violet R and reactive blue 2 were the most active compounds having selective indices of greater than 30 and EC50 values of 4-30 microM. When tested against a clinical isolate, the 4 compounds were 2- to 5-fold less active. The antiviral activity was distinctly separate from the virucidal activity (> 1000 microM). The compounds were weakly toxic to either log phase or stationary cells in most of the following cytotoxicity assays: neutral red uptake assay, lactic acid dehydrogenase assay, trypan blue exclusion assay and radiolabeled macromolecular precursor uptake assays. Using a genotoxicity assay, the comet assay, only reactive blue 2 and acid black 48 were found to cause DNA strand breakage. This occurred at concentrations of 30 and 170 microM, respectively. These results suggest that these compounds could be a prototype for synthesizing even more effective HCMV-inhibitory anthraquinone derivatives.
Barnard
D L
DL
Department of A.D.V.S., Utah State University, Logan 84322-5600, USA.
Fairbairn
D W
DW
O'Neill
K L
KL
Gage
T L
TL
Sidwell
R W
RW
D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects*; D003588:Cytopathogenic Effect, Viral; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
D000880:Anthraquinones; D000998:Antiviral Agents