Rebeccamycin is an indolocarbazole class inhibitor of topoisomerase I. In the course of structure-activity relationship studies on rebeccamycin derivatives, we have synthesized analogs with the sugar moiety attached to either one or both indole nitrogens. Some analogs, especially those with substitutions at the 6' position of the carbohydrate moiety, exhibit potent inhibitory activity toward checkpoint kinase 1 (Chk1), a kinase that has a major role in the G(2)/M checkpoint in response to DNA damage. Some of these compounds retained a genotoxic activity either through intercalation into the DNA and/or by topoisomerase I-mediated DNA cleavage. We explored the structure-activity relationship between these compounds and their multiple targets. These rebeccamycin derivatives represent a novel class of potential antitumor agents that have a dual effect and might selectively induce the death of cancer cells.