Heterocyclic Quinones. 4. A new highly cytotoxic drug: 6,7-bis(1-aziridinyl)-5,8-quinazolinedione
| Autor: | Michel Baron, Emmanuelle Voisin, S. Cros, Sylviane Giorgi-Renault, Jean Renault, Claude Paoletti, P. Mailliet |
|---|---|
| Rok vydání: | 1983 |
| Předmět: |
DNA damage
Stereochemistry Leukemia P388 Mutagenicity Tests Antineoplastic Agents medicine.disease In vitro Ames test chemistry.chemical_compound Electrophilic substitution Leukemia Mice Streptonigrin chemistry Drug Discovery Nucleophilic substitution medicine Quinazolines Molecular Medicine Animals Cytotoxicity Leukemia L1210 Sarcoma 180 |
| Zdroj: | Journal of medicinal chemistry. 26(12) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|