Substituted 4,5'-Bithiazoles as Catalytic Inhibitors of Human DNA Topoisomerase IIα.

ABSTRACT: Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class of substituted 4,5'-bithiazoles as catalytic inhibitors targeting the human DNA topoisomerase IIα. Based on a structural comparison of the ATPase domains of human and bacterial type II topoisomerase, a focused chemical library of 4,5'-bithiazoles was assembled and screened to identify compounds that better fit the topology of the human topo IIα adenosine 5'-triphosphate (ATP) binding site. Selected compounds showed inhibition of human topo IIα comparable to that of the etopos

SUBMITTER: Bergant Loboda K 

PROVIDER: S-EPMC7469689 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature