کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1399040 | 1501147 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis, cytotoxicity and DNA binding of oxoazabenzo[de]anthracenes derivatives in colon cancer Caco-2 cells Synthesis, cytotoxicity and DNA binding of oxoazabenzo[de]anthracenes derivatives in colon cancer Caco-2 cells](/preview/png/1399040.png)
• Copper mediated cyclisation of 1,8-dihydroxyanthraquinone.
• Substrates include a series of aminoalcohols and n-alkyl aliphatic heterocycles.
• Piperidino derivative displayed comparable cytotoxicity to doxorubicin upon 72 h incubation.
• Indirect inhibition of topoisomerase enzymes.
New oxoazabenzo[de]anthracenes derivatives were synthesised and characterised. Their interactions with calf thymus DNA were studied by UV spectrophotometric analysis and a competitive ethidium bromide displacement assay. Cytotoxicity was determined by MTT assay, against colon adenocarcinoma (Caco-2 cells). Among all the oxoazabenzo[de]anthracenes derivatives reported herein only the piperidino derivative exhibited strong DNA binding properties and cytotoxic activity with IC50 values in the range of 16 ± 1.5 μM (72-h treatment). In addition, the piperidino derivative did not directly inhibit topoisomerase I and topoisomerase II enzymes. The results confirm that the presence of the oxoazabenzo[de]anthracenes together with the piperidino functionality is crucial in exerting DNA binding and cytotoxic properties, hence demonstrating promise as a chemical scaffold for further development of new anticancer agents.
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Journal: European Journal of Medicinal Chemistry - Volume 69, November 2013, Pages 754–761