Anti-human cytomegalovirus activity and toxicity of sulfonated anthraquinones and anthraquinone derivatives

• Published in: Antiviral research 1995-12, Vol.28 (4), p.317-329
• Main Authors: Barnard, D.L., Fairbairn, D.W., O'Neill, K.L., Gage, T.L., Sidwell, R.W.
• Format: Article
• Language: English
• Subjects: Anthraquinone; Anthraquinones - chemistry; Anthraquinones - pharmacology; Anthraquinones - toxicity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agent; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - toxicity; Biological and medical sciences; Cells, Cultured; Comet assay; Cytomegalovirus - drug effects; Cytopathogenic Effect, Viral; DNA Damage; Fibroblasts - drug effects; Genotoxicity assay; Human cytomegalovirus; Humans; Medical sciences; Pharmacology. Drug treatments; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/0166-3542(95)00057-7

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 EC 50 values of 4–30 μM. 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 μM). 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 μM, respectively. These results suggest that these compounds could be a prototype for synthesizing even more effective HCMV-inhibitory anthraquinone derivatives.