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Identification of potent catalytic inhibitors of human DNA topoisomerase II by structure-based virtual screening.

ABSTRACT: Human DNA topoisomerase II (Top2) is a promising target for cancer treatment. To overcome the limitations of known Top2 inhibitors, novel Top2 catalytic inhibitors with new scaffolds were identified by structure-based virtual screening. In particular, compound 8 showed good in vitro antiproliferative activity with a broad spectrum. Top2-mediated cleavage assay and molecular modeling rationalized the mode of action. The new Top2 inhibitors are considered as good starting points for further hit-to-lead optimization in anticancer drug discovery.

SUBMITTER: Dong G

PROVIDER: S-EPMC6071756 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Identification of potent catalytic inhibitors of human DNA topoisomerase II by structure-based virtual screening.

Dong Guoqiang G Wu Ying Y Sun Ying Y Liu Na N Wu Shanchao S Zhang Wannian W Sheng Chunquan C

MedChemComm 20180524 7

Human DNA topoisomerase II (Top2) is a promising target for cancer treatment. To overcome the limitations of known Top2 inhibitors, novel Top2 catalytic inhibitors with new scaffolds were identified by structure-based virtual screening. In particular, compound <b>8</b> showed good <i>in vitro</i> antiproliferative activity with a broad spectrum. Top2-mediated cleavage assay and molecular modeling rationalized the mode of action. The new Top2 inhibitors are considered as good starting points for ...[more]

PMID: 30109001

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