Heterocyclic quinones. 17. A new in vivo active antineoplastic drug: 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8- quinazolinedione.
A series of heterocyclic quinones, 6-substituted and 6,7-disubstituted 4-(alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that have been prepared and studied for the structure-activity relationship, the most potent cytotoxic compound on L1210 leukemia cells was the 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8- quinazolinedione (24). This compound has been tested with the use of a cell-image processor on MCF-7 human mammary and HBL human melanoma cell lines. The results show that compound 24 influences cell proliferation and blocks both cells lines in the S phase. In vivo antineoplastic activity of compound 24 has been demonstrated on a broad spectrum of murine experimental models, but it was found highly toxic and produced long-delayed deaths.
Giorgi-Renault
S
S
Département de Chimie Organique, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Renault
J
J
Gebel-Servolles
P
P
Baron
M
M
Paoletti
C
C
Cros
S
S
Bissery
M C
MC
Lavelle
F
F
Atassi
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007939:Leukemia L1210; D007942:Leukemia, Experimental / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001388:Aziridines; D011799:Quinazolines; C067054:6,7-bis(1-aziridinyl)-4-((3-(N,N-dimethylamino)propyl)amino)-5,8-quinazolinedione