New Copper (II), Palladium (II), and Platinum (II) 2-Acetylpyrazine Tert-Butylthiosemicarbazone Complexes: Inhibition of Human Topoisomerase IIα and Activity against Breast Cancer Cells
Open Access
- 1 January 2022
- journal article
- research article
- Published by Scientific Research Publishing, Inc. in Open Journal of Medicinal Chemistry
- Vol. 12 (01), 1-13
- https://doi.org/10.4236/ojmc.2022.121001
Abstract
The new ligand, 2-acetylpyrazine-tertbutylthiosemicarbazone (APZ-tBTSC), and its Cu(II), Pd(II) and Pt(II) complexes have been synthesized. This ligand coordinates to the metal ions in a tridentate monoanionic fashion forming monometallic complexes with the formula [M(APZ-tBTSC)Cl]. The ligand and the three metal complexes [Cu(APZ-tBTSC)Cl], [Pd(APZ-tBTSC)Cl], and [Pt(APZ-tBTSC)Cl] were tested for anti-proliferative biological behavior with a panel of seven microbes, and the copper and palladium complexes were found to be highly active against Gram positive bacteria. The 4 compounds were also tested in human topoisomerase IIα DNA relaxation assays and all three metal complexes had topoisomerase inhibition at a concentration between 4 - 6 micro-molar. The 4 compounds were also tested for activity with the HEK293T cell line and also the breast cell cancer line, MDA-MB-231. The most effective compound for activity against the HEK293T cell line was the [Cu(APZ-tBTSC)Cl] complex, and the MDA-MB-231 breast cancer cell line was the [Pt(APZ-tBTSC)Cl] complex.Keywords
This publication has 18 references indexed in Scilit:
- Examination of the Impact of Copper(II) α-(N)-Heterocyclic Thiosemicarbazone Complexes on DNA Topoisomerase IIαChemical Research in Toxicology, 2016
- The anticancer thiosemicarbazones Dp44mT and triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIαBiochemical Pharmacology, 2012
- Role of Metalation in the Topoisomerase IIα Inhibition and Antiproliferation Activity of a Series of α-Heterocyclic-N4-Substituted Thiosemicarbazones and Their Cu(II) ComplexesJournal of Medicinal Chemistry, 2011
- Novel Thiosemicarbazones of the ApT and DpT Series and Their Copper Complexes: Identification of Pronounced Redox Activity and Characterization of Their Antitumor ActivityJournal of Medicinal Chemistry, 2010
- Thiosemicarbazones from the Old to New: Iron Chelators That Are More Than Just Ribonucleotide Reductase InhibitorsJournal of Medicinal Chemistry, 2009
- A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cellsInvestigational New Drugs, 2007
- Phase II study of Triapine® in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161)Investigational New Drugs, 2007
- Main group metal complexes of semicarbazones and thiosemicarbazones. A structural reviewCoordination Chemistry Reviews, 2000
- Transition metal complexes of semicarbazones and thiosemicarbazonesCoordination Chemistry Reviews, 1985
- Klinische und experimentelle Studien zur ThiosemicarbazonwirkungNaunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1950