Structure-activity relationships of a series of antitumoral 5,8-quinazolinediones in mutagenicity studies.
Four antitumoral 5,8-quinazolinediones were examined for their ability to induce mutation in Salmonella typhimurium. Each compound was tested at several concentrations in 4 strains. Relationships were established between the structure of the quinones and their mutagenic activities. The mutagenicity was influenced by (i) the nature of the substituent(s) of the quinonic moiety: the methoxyquinone had no mutagenic properties and the aziridinylquinones were mutagenic in the 4 strains with or without activation by S9 mix; (ii) the presence or the absence of a diaminopolymethylenic chain in the 4 position; (iii) the monomeric or the dimeric structure of the tested compound. Interestingly, the data indicated that the aziridinylquinazolinedione bearing the dimethylaminopropylamino chain in the 4 position was less mutagenic and had greater antitumor activity than the dimeric quinone.
Callais
F
F
Laboratoire d'Hygiène et de Santé Publique, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Min
S
S
Giorgi-Renault
S
S
Festy
B
B
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001388:Aziridines / Q000737:chemistry / Q000633:toxicity*; D008110:Liver Extracts; D009152:Mutagenicity Tests; D011799:Quinazolines / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001388:Aziridines; D008110:Liver Extracts; D011799:Quinazolines; C067054:6,7-bis(1-aziridinyl)-4-((3-(N,N-dimethylamino)propyl)amino)-5,8-quinazolinedione