| Acridones have long been known as antiviral agents but until recently have been neglected for antiviral drug development. Within the last few years many groups have reevaluated their ability to prevent viral infection. In this study, several dihydroxy acridones are synthesized and evaluated. These compounds are tested to determine their activity in the prevention of herpes simplex viruses one and two. Additionally, structure-activity relationships are established to determine the necessity of the dihydroxy substituents. Moreover, SAR of the central ring is presented showing that other tricyclic heterocycles can be used to prevent viral infection. Several compounds are found to show activity for the prevention of human immunodeficiency virus in peripheral blood mononuclear cells. Lastly, three potential mechanisms of action are presented. These consist of intercalation into viral or cellular RNA or DNA to prevent certain stages of the viral life cycle; inhibition of viral encapsidation and egress; or inhibition of viral attachment to the cell by blocking heparin sulfate. The final theory is tested by in vitro heparin binding experiments and the theory is found to be without merit. Finally, preliminary data is presented on attempts to develop acridine antiviral agents. |
