TITLE:
New Copper (II), Palladium (II), and Platinum (II) 2-Acetylpyrazine Tert-Butylthiosemicarbazone Complexes: Inhibition of Human Topoisomerase IIα and Activity against Breast Cancer Cells
AUTHORS:
Edward C. Lisic, Sarah N. Grossarth, Sarah B. Bowman, Jessica L. Hill, Michael W. Beck, Joseph E. Deweese, Xiaohua Jiang
KEYWORDS:
Topoisomerase, Breast Cancer, α-(N)-Heterocyclic Thiosemicarbazones
JOURNAL NAME:
Open Journal of Medicinal Chemistry,
Vol.12 No.1,
March
31,
2022
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.