Heterocyclic quinones. 4. A new highly cytotoxic drug: 6,7-bis(1-aziridinyl)-5,8-quinazolinedione
- 1 December 1983
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 26 (12) , 1715-1719
- https://doi.org/10.1021/jm00366a011
Abstract
In order to obtain 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 [mouse] cells in vitro. One of them, 6,7-bis(1-aziridinyl)-5,8-quinazolinedione, which exhibits a high cytotoxic activity (ID50 = 0.08 .mu.M), was further screened in standard antitumor systems, inactive on other experimental models. This compound was highly mutagenic for Salmonella typhimurium TA98 and TA100 strains (Ames test), suggesting that DNA damage could be responsible for its cytotoxicity.This publication has 1 reference indexed in Scilit:
- Synthetic studies of the antitumor antibiotic streptonigrin. I. Synthesis of the A‐B ring portion of streptonigrinJournal of Heterocyclic Chemistry, 1976