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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.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Giorgi-Renault S,Renault J,Gebel-Servolles P,Baron M,Paoletti C,Cros S,Bissery MC,Lavelle F,Atassi G

doi

10.1021/jm00105a007

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

38-46

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

34

pub_type

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