20.500.12556/RUL-144331 ATP-competitive inhibitors of human DNA topoisomerase IIα with improved antiproliferative activity based on N-phenylpyrrolamide scaffold ATP-competitive inhibitors of human DNA topoisomerase II show potential for becoming the successors of topoisomerase II poisons, the clinically successful anticancer drugs. Based on our recent screening hits, we designed, synthesized and biologically evaluated new, improved series of N-phenylpyrrolamide DNA topoisomerase II inhibitors. Six structural classes were prepared to systematically explore the chemical space of N-phenylpyrrolamide based inhibitors. The most potent inhibitor, 47d, had an IC$_{50}$ value of 0.67 μM against DNA topoisomerase IIα. Compound 53b showed exceptional activity on cancer cell lines with IC$_{50}$ values of 130 nM against HepG2 and 140 nM against MCF-7 cancer cell lines. The reported compounds have no structurally similarity to published structures, they are metabolically stable, have reasonable solubility and thus can serve as promising leads in the development of anticancer ATP-competitive inhibitors of human DNA topoisomerase IIα. anticancer drugs ATP-competitive inhibitors catalytic inhibitor cytotoxicity human DNA topoisomerase II ATP-kompetitivni katalitični zaviralec človeška DNA topoizomeraza II rak medicina farmacevtska kemija citotoksičnost true false true Angleški jezik Slovenski jezik Članek v reviji 2023-02-15 08:02:49 2023-02-15 08:02:52 2023-08-30 10:58:22 0000-00-00 00:00:00 2023 0 0 21 str. Vol. 249, art. 115116 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.27:615.28 0223-5234 10.1016/j.ejmech.2023.115116 141491715 1-s2.0-S0223523423000314-main.pdf 1-s2.0-S0223523423000314-main.pdf 1 90814CBB076E27245E9784A10AB17FB7 3cc7dccccc8c2e76c9134d1e3d225bb5251f3ebb1ec7c63c50d9bce50fed1fcd b82b43cb-acfe-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166588 https://www.sciencedirect.com/science/article/pii/S0223523423000314 0 7052d3f9-acfe-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166587 Fakulteta za farmacijo 0 0 0