Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines |
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Authors: | Xiao Xiangshu Miao Ze-Hong Antony Smitha Pommier Yves Cushman Mark |
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Institution: | Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, IN 47907, USA. |
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Abstract: | Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase I (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top1. Through COMPARE analysis, cytotoxicity studies in Top1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells. |
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