Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
12 11 2020
12 11 2020
Historique:
pubmed:
21
10
2020
medline:
19
12
2020
entrez:
20
10
2020
Statut:
ppublish
Résumé
We disclose a novel class of 6-amino-tetrahydroquinazoline derivatives that inhibit human topoisomerase II (topoII), a validated target of anticancer drugs. In contrast to topoII-targeted drugs currently in clinical use, these compounds do not act as topoII poisons that enhance enzyme-mediated DNA cleavage, a mechanism that is linked to the development of secondary leukemias. Instead, these tetrahydroquinazolines block the topoII function with no evidence of DNA intercalation. We identified a potent lead compound [compound
Identifiants
pubmed: 33079544
doi: 10.1021/acs.jmedchem.0c00774
pmc: PMC7668297
mid: NIHMS1642693
doi:
Substances chimiques
Isoenzymes
0
Topoisomerase II Inhibitors
0
hydroquinidine
8P68XPY4HG
DNA
9007-49-2
DNA Topoisomerases, Type II
EC 5.99.1.3
Quinidine
ITX08688JL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12873-12886Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM126363
Pays : United States
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