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The antiherpesvirus activity of 14 derivatives of indoloquinoxaline was tested. The most active was 2,3-dimethyl(dimethylaminoethyl)5H-indolo-(2,3-b)quinoxaline, also called B-220. The antiherpesvirus mechanism of B-220 was sought. The compound inhibited replication of herpes simplex virus type 1, cytomegalovirus, and varicella-zoster virus in tissue culture at concentrations of 1 to 5 ,uM, depending on the cell type used for assay and the amount of virus. Cellular toxicity was seen at a concentration of 10 to 30 ,uM, and antiviral Several condensed-ring systems containing indole have antiviral activity (6). Such compounds are distantly related to ellipticin and quinacrines, which are known to intercalate in DNA (for a review, see reference 11). Compounds in the 6H-indolo-(2,3-b)quinoxaline series were synthesized, and their effect on herpesviruses was assayed in different cells. The most active compound, 2,3-dimethyl(dimethyl aminoethyl)5H-indolo-(2,3-b)quinoxaline (B-220), was further tested for antiviral effect and mechanism of action. IndQloquinoxalines in high concentrations (around 300 ,uM) inactivate virions, while at lower concentrations (around 3 FM), synthesis of viral DNA and protein appears to be reduced. B-220 was tested against herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), and varicella-zoster virus (VZV). A comparison was made with three previously known active substances: acyclovir (ACV; 3) for HSV-1, phosphonoformate (PFA; 15) for CMV, and the guanosine analog (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (1) for VZV. MATERIALS AND METHODSCompounds. B-220 (Fig. 1)

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