Type II topoisomerases are ubiquitous enzymes that are required for proper chromosome segregation as well as DNA replication, transcription, and recombination. Beyond their critical physiological functions, topoisomerase IIa and IIb are the primary targets for some of the most active and widely prescribed anticancer drugs in clinical use. We previously reported that 3-trifluoromethylated 9-amino-3,4-dihydroacridin-1 (2H)-ones act as covalent poisons of human topoisomerase IIα. In another study we replaced the 3-trifluoromethyl group with a 3-phenyl group. Although the above derivative lacked the 9-amino functionality it displayed high potency in NCI’s panel of 60 cancer cell lines in five dose screening test. Our current study involves lead compound optimization particularly on the 3-phenyl group. The synthesis, in vitro cytotoxicity, molecular docking and ADME properties of the compounds will be presented.

Synthesis, SAR, and <i>in silico</i> ADME screening studies of some 9-amino-3-phenylacridone derivatives as topoisomerase II inhibitors

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Synthesis, SAR, and in silico ADME screening studies of some 9-amino-3-phenylacridone derivatives as topoisomerase II inhibitors