ATP-competitive inhibitors of human DNA topoisomerase IIα with improved antiproliferative activity based on N-phenylpyrrolamide scaffold

Žiga Skok (Avtor), Martina Durcik (Avtor), Živa Zajec (Avtor), Darja Gramec (Avtor), Krištof Bozovičar (Avtor), Anja Pišlar (Avtor), Tihomir Tomašić (Avtor), Anamarija Zega (Avtor), Lucija Peterlin-Mašič (Avtor), Danijel Kikelj (Avtor), Nace Zidar (Avtor), Janez Ilaš (Avtor)

Povzetek

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 IC50 value of 0.67 μM against DNA topoisomerase IIα. Compound 53b showed exceptional activity on cancer cell lines with IC50 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.

Ključne besede

ATP-kompetitivni katalitični zaviralec;človeška DNA topoizomeraza II;anticancer;ATP-competitive;Catalytic inhibitor;cytotoxic;human DNA topoisomerase II;

Podatki

Jezik:	Angleški jezik
Leto izida:	2023
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL FFA - Fakulteta za farmacijo
UDK:	577.27:615.28
COBISS:	141491715
ISSN:	0223-5234
Št. ogledov:	186
Št. prenosov:	34
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	Rak (medicina);Farmacevtska kemija;Citotoksičnost;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 1-21
Zvezek:	ǂVol. ǂ249
Čas izdaje:	2023
DOI:	10.1016/j.ejmech.2023.115116
ID:	18011582