Design, Synthesis, and DNA-Binding of N-Alkyl(anilino)quinazoline Derivatives
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- 作者：Antonio Garofalo ; Laurence Goossens ; Brigitte Baldeyrou ; Amlie Lemoine ; Sverine Ravez ; Perrine Six ; Marie-Hlne David-Cordonnier ; Jean-Paul Bonte ; Patrick Depreux ; Amlie Lansiaux ; Jean-Franois Goossens
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：November 25, 2010
- 年：2010
- 卷：53
- 期：22
- 页码：8089-8103
- 全文大小：1302K
- 年卷期：v.53,no.22(November 25, 2010)
- ISSN：1520-4804
文摘
New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared from 4-chloro-6,7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a−c, 16a,b, and 17a,b), (aminophenyl)ureas (12a,b and 13a−f), anilines (4a−m, 20a,b), N-alkyl(aniline) (5a−m, 21a,b, 22a,d), and N-aminoalkyl(aniline) (22e−g) have been synthesized. These molecules were evaluated for their cytotoxic activities and as potential DNA intercalating agents. We studied the strength and mode of binding to DNA of these molecules by DNA melting temperature measurements, fluorescence emission, and circular dichroism. The results of various spectral and gel electrophoresis techniques obtained with the different compounds, in particular compounds 5g and 22f, revealed significant DNA interaction. These experiments confirm that the N-aminoalkyl(anilino)-6,7-dimethoxyquinazoline nucleus is an efficient pharmacophore to trigger binding to DNA, via an intercalative binding process.