Pyrimido[4,5- g ]quinazoline quinone derivatives were synthesized as anthraquinone-like reductive alkylating agents. Like many naturally-occurring antibiotics, these quinone derivatives are designed to afford an alkylating quinone methide species upon reduction and leaving group elimination. Kinetic studies of pyrimido[4,5- g ]quinazoline hydroquinones provided evidence of quinone methide intermediates able to trap nucleophiles (alkylation) and protons. The rate of quinone methide formation is determined by the hydroquinone free energy. Thus, a linear free energy relationship for quinone methide formation was obtained by plotting rates of quinone methide formation, as the log, versus the quinone reduction potential. The pyrimido[4-5- g ]quinazoline quinone methides fall on this free energy plot, showing that these species are formed by the same mechanism as the other structurally-diverse quinone methides previously studied in this research group. A drawback of many quinone antibiotics, particularly the anthracyclines, is the formation of toxic oxygen species by quinone/hydroquinone cycling. In the present invention pyrimido[4,5- g ]quinazoline hydroquinones are found to be relatively stable toward oxygen, and thus cause little oxygen toxicity. Antitumor screening revealed that the disclosed pyrimid [4,5- g ] quinazoline dione and tetione derivatives possess excellent inhibitory activity against selected human cancer cell lines.