Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine

被引：24

作者：

Benchabane, Yohann ^{[2
]}

Di Giorgio, Carole ^{[1
]}

Boyer, Gerard ^{[2
]}

Sabatier, Anne-Sophie ^{[1
]}

Allegro, Diane ^{[3
]}

Peyrot, Vincent ^{[3
]}

De Meo, Michel ^{[1
]}

机构：

[1] Univ Aix Marseille, Lab Biogenotoxicol & Mutagenese Environm, EA 1784, Fac Pharm,ECCOREV,FR 3098, F-13385 Marseille 05, France

[2] Univ Paul Cezanne, Fac St Jerome, iSm2, Lab HIT,UMR 6263, F-13397 Marseille 20, France

[3] Univ Aix Marseille, Fac Pharm, INSERM, CRO2,U91, F-13385 Marseille 05, France

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 06期

关键词：

Proflavine derivatives; Phototoxicity; Photogenotoxicity; Micronucleus assay; DNA; DERIVATIVES;

D O I：

10.1016/j.ejmech.2009.01.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong non-clastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：2459 / 2467

页数：9

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