کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1360268 981432 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The structure-based design, synthesis, and biological evaluation of DNA-binding amide linked bisintercalating bisanthrapyrazole anticancer compounds
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
The structure-based design, synthesis, and biological evaluation of DNA-binding amide linked bisintercalating bisanthrapyrazole anticancer compounds
چکیده انگلیسی

A series of amide-coupled bisanthrapyrazole derivatives of 7-chloro-2-[2-[(2-hydroxyethyl)methylamino]ethyl]anthra[1,9-cd]pyrazol-6(2H)-one (AP9) were designed using molecular modeling and docking and synthesized in order to develop an anticancer drug that formed a strongly binding bisintercalation complex with DNA. Concentration dependency for the increase in the DNA melting temperature was used to determine the DNA binding strength and whether bisintercalation occurred for the newly synthesized analogs. The ability of the compounds to inhibit the growth of the human erythroleukemic K562 cell line and inhibit the decatenation activity of DNA topoisomerase IIα was also measured. Finally, the compounds were evaluated for their ability to act as topoisomerase II poisons by measuring the topoisomerase IIα-mediated double strand cleavage of DNA. All of the bisanthrapyrazoles inhibited K562 cell growth and topoisomerase IIα in the low micromolar range. Compounds with either two or three methylene linkers formed bisintercalation complexes with DNA and bound as strongly as, or more strongly than, doxorubicin. In conclusion, a novel group of amide-coupled bisintercalating anthrapyrazole compounds were designed, synthesized, and evaluated for their physico-chemical and biologic properties as potential anticancer agents.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 13, 1 July 2009, Pages 4575–4582
نویسندگان
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