DNA binding, anti-tumour activity and reactivity toward cell thiols of acridin-9-ylalkenoic derivatives

Journal of Chemical Sciences

M Burikova³  M Prokaiova¹  J Imrich¹  O Salem²  A Grolmusova³  M Vilkova¹  J Plsikova²  H Paulikova³  M Kozurkova1² 

[1] Department of Organic Chemistry, P J Å afárik University in Kosice, Faculty of Science, Moyzesova 11, SK-04001 Kosice$$;Department of Biochemistry, P J Å afárik University in Kosice, Faculty of Science, Moyzesova 11, SK-04001 Kosice$$;Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak Technical University, Radlinského 9, SK-81237 Bratislava, Slovak Republic$$

关键词: DNA binding;    anti-tumour activity;    acridin-9-ylalkenoic derivatives;    glutathione.;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

In this paper, we describe the synthesis, biochemical properties and biological activity of a series of new 9-substituted acridine derivatives with a reactive alkene moiety: 9-[(E)-2-phenylethenyl] acridine (1) and methyl (2E)-3-(acridin-9-yl)-prop-2-enoate (2). The interaction of derivatives 1 and 2 with calf thymus DNA was investigated using UV-Vis, fluorescence and circular dichroism spectroscopy. The binding constants K were estimated as being in the range of 1.9 to 7.1 × 105 M−1, and the percentage of hypochromism was found to be 40–57% (from spectral titration). UV-Vis, fluorescence, and CD measurements indicate that the compounds were effective DNA-intercalating agents. Electrophoretic separation proved that ligands 1 and 2 relaxed topoisomerase I at a concentration of 5 𝜇M. Ester 2 was shown to have a stronger cytostatic effect on leukemia cell line L1210 than alkene 1. The incubation of ligands 1 and 2 with the ovarian carcinoma cell line A2780 confirmed their extensive cytotoxic effects, an effect which was particularly pronounced in the case of ligand 2. Cytotoxicity tests against A2780 cells demonstrate that a conjugate of compound 2 with 𝐿-cysteine (3) is less cytotoxic than compound 2, especially at concentrations greater than 10 𝜇M.

【 授权许可】

Unknown