New spiro tria(thia)zolidine-acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds

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• 作者：Othman M. Salem^a ; M&aacute ; ria Vilkov&aacute ; ^b ; Jana Janočkov&aacute ; ^a ; ^d ; Rastislav Jendželovský ; ^c ; Peter Fedoročko^c ; Eva Žileck&aacute ; ^a ; Jana Ka&scaron ; p&aacute ; rkov&aacute ; ^e ; Viktor Brabec^e ; J&aacute ; n Imrich^b ; M&aacute ; ria Kožurkov&aacute ; ^a ; ^d ; ^{maria.kozurkova@upjs.sk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Spiroacridine derivatives ; Topoisomerases I and II ; HL-60 cells ; DNA-binding
• 刊名：International Journal of Biological Macromolecules
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：86
• 期：Complete
• 页码：690-700
• 全文大小：1756 K

文摘

Three new diphenylsubstituted spirotriazolidine- and thiazolidinone–acridines were prepared and their interaction with calf thymus DNA investigated with UV–vis, fluorescence, circular dichroism spectroscopy and viscometry. The binding constants K were estimated to range from 0.34 to 0.93 × 10⁴ M⁻¹. UV–vis, fluorescence and circular dichroism measurements indicated that the compounds act as effective DNA-interacting agents. Electrophoretic separation proved that ligands inhibited topoisomerase I and II. The biological activity of compounds 3, 5 & 6 at several different concentrations (10, 20 and 50 μM) was evaluated both 48 h and 72 h following their addition to HL-60 cancer cells. The results were analysed using various different techniques (MMP detection, changes in metabolic activity/viability and analysis of cell cycle distribution). Acridine was also used as the positive control in these assays. The results from MMP analysis demonstrate the strong effect of 3-diphenylamino-2-(acridin-9-yl)imino-1,3-thiazolidin-4-one (5) on mitochondrial physiology. Cell viability analysis showed that acridine derivatives 3 and 6 were less effective than derivative 5 and the acridine control.