Human topoisomerase IB is a target of a thiosemicarbazone copper(II) complex

• HPyCT4BrPh efficiently inhibits topoisomerase IB after copper coordination.
• [Cu(PyCT4BrPh)Cl] inhibits topoisomerase IB enzyme in a dose dependent manner.
• [Cu(PyCT4BrPh)Cl] acts on the cleavage and religation steps of the enzyme catalytic cycle.

The human topoisomerase IB inhibition and the antiproliferative activity of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone HPyCT4BrPh alone and its copper(II) complex [Cu(PyCT4BrPh)Cl] was investigated. [Cu(PyCT4BrPh)Cl] inhibits both the DNA cleavage and religation step of the enzyme, whilst the ligand alone does not display any effect. In addition we show that coordination to copper(II) improves the cytotoxicity of HPyCT4BrPh against THP-1 leukemia and MCF-7 breast cancer cells. The data indicate that the copper(II) thiosemicarbazone complex may hit human topoisomerase IB and that metal coordination can be useful to improve cytotoxicity of this versatile class of compounds.

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