Zn(II) and Co(II) derivatives anchored with scorpionate precursor: Antiproliferative evaluation in human cancer cell...

A 'scorpionate' type precursor [bdtbpza = bis(3,5-di-t-butylpyrazol-1-yl)acetate] has been employed to synthesize two mononuclear Zn^II and Co^II derivatives, namely [Zn(bdtbpza)₂ (H₂O)₂]·2.5CH₃OH·2[(CH₃)₃C-C₃H₂N₂-C(CH₃)₃] (1) and [Co(bdtbpza)₂(CH₃OH)₄] (2) in good yield. Single crystal X-ray diffraction analysis reveals that in 1, the Zn^II atom is tetrahedrally surrounded by a pair of O_acetate atoms of two bis(pyrazol-1-yl)acetate units and two water molecules; while in 2, the Co^II atom shows an octahedral environment coordinating a pair of O_acetate atoms of two bis(pyrazol-1-yl)acetate units along with four methanol molecules. The EPR spectra of 2 recorded at 77 and 298 K confirmed the tetragonal symmetry of the high spin Co(II). The DFT (Density functional theory) computation is in good agreement with the geometry proposed for compounds 1 and 2. Both the compounds display a high antiproliferative activity against HCT116 (colorectal carcinoma) and A2780 (ovarian carcinoma) cell lines compared to human normal dermal fibroblasts. In the case of A2780 cells, compounds 1 and 2 exhibit IC₅₀ values that are similar to those described for cisplatin, a widely used chemotherapeutic drug. Exposure of A2780 cells to the IC₅₀ concentration of each compound led to an increase of the number of apoptotic and autophagic cells. In the case of compound 1, the accumulation of intracellular ROS (Reactive oxygen species) is responsible for triggering A2780 cell death.