کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1357382 981246 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons
چکیده انگلیسی

Fluorine and chlorine are metabolically stable, but generally less active replacements for a nitro group at the 3-position of indenoisoquinoline topoisomerase IB (Top1) poisons. A number of strategies were employed in the present investigation to enhance the Top1 inhibitory potencies and cancer cell growth inhibitory activities of halogenated indenoisoquinolines. In several cases, the new compounds’ activities were found to rival or surpass those of similarly substituted 3-nitroindenoisoquinolines, and several unusually potent analogs were discovered through testing in human cancer cell cultures. A hydroxyethylaminopropyl side chain on the lactam nitrogen of two halogenated indenoisoquinoline Top1 inhibitors was found to also impart inhibitory activity against tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes that participate in the repair of DNA damage induced by Top1 poisons.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 24, Issue 7, 1 April 2016, Pages 1469–1479
نویسندگان
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