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With the aim of obtaining new antitumor drugs more active than previously described 11H-indolo[3,2-c]quinoline-1,4-diones and 7,8,9,10-tetrahydro-11H-indolo[3,2-c]quinoline-1,4-diones, the synthesis and activities of a series of 3-substituted 11H-pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones and of 7,8,9,10-tetrahydro-11H-pyrido-[3',4':4,5]pyrrolo[3,2-c] quinoline-1,4-diones were studied. Some quinones were more cytotoxic in vitro towards L1210 leukemia cells but were not active in vivo towards murine P388 leukemia.

With the aim of obtaining new antitumoral agents, a series of 5,8-quinazolinediones was prepared. 5-Amino-6-methoxyquinazoline was oxidized by Fremy's salt to give 6-methoxy-5,8-quinazolinedione. Nucleophilic substitution reaction at C6, electrophilic substitution at C7, and synthesis of 7-amino-6-methoxy-5,8-quinazolinedione, the parent compound of streptonigrin, were studied. These compounds were tested for cytotoxic properties on L1210 leukemia cells in vitro. One of them, 6,7-bis(1-aziridinyl)-5,8-quinazolinedione, which exhibits a high cytotoxic activity (ID50 = 0.08 microM), was further screened in standard antitumor systems, including L1210 leukemia, P388 lymphocytic leukemia, sarcoma 180, and B16 melanocarcinoma. This drug gives a significant antitumoral effect on P388 leukemia but is inactive on other experimental models. Moreover, this compound was found to be highly mutagenic for Salmonella typhimurium TA98 and TA100 strains (Ames test), suggesting that DNA damage could be responsible for its cytotoxicity.