Heterocyclic Quinones. 4. A new highly cytotoxic drug: 6,7-bis(1-aziridinyl)-5,8-quinazolinedione.
J Med Chem
; 26(12): 1715-9, 1983 Dec.
Article
en En
| MEDLINE
| ID: mdl-6644740
ABSTRACT
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.
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Bases de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1983
Tipo del documento:
Article