Combined effects of electroporation and 100 mGy X-ray on the anticancer activity of newly synthesized niraparib-based Schiff base, Pd(II) and Fe(II) complexes in SKOV-3 cancer cells

Abstract

A novel niraparib-derived Schiff base (Sb) ligand and its Pd(II) and Fe(II) complexes were synthesized and comprehensively characterized using elemental and thermal analyses, 1H, 13C NMR, FT-IR, UV-Vis, magnetic susceptibility, mass spectrometry, and powder X-ray diffraction (XRD). The spectroscopic and magnetic data supported the proposed square-planar and octahedral geometries for the Pd(II) and Fe(II) complexes, coordinated through nitrogen and oxygen donor atoms. PXRD analysis revealed that both complexes exhibited amorphous structures. The anticancer activities of the synthesized compounds were evaluated in the SKOV-3 ovarian cancer cell line using chemotherapy, electrochemotherapy (ECT), and ECT combined with low-dose ionizing radiation (IR, 100 mGy), either individually or in combination, while biocompatibility was evaluated in human dermal fibroblast (HDF) cells using the MTT assay. The Fe(II) and Pd(II) complexes exhibited superior cytotoxic activity against SKOV-3 cells compared to the conventional chemotherapeutic agent carboplatin, as evidenced by significantly lower IC50 values (26.42 and 38.47 mu M, respectively) than that of carboplatin (52.08 mu M). Our findings indicate that electroporation (EP) significantly enhanced the anticancer efficacy of both the reference drug and newly synthesized complexes. Furthermore, the application of 100 mGy X-rays further potentiated this effect, with the greatest therapeutic efficacy observed for the ECT + 100 mGy X-ray combination. These findings suggest that niraparib-derived Schiff base metal complexes, particularly the Fe(II) complex, are promising candidates for anticancer drug development, especially in combination with ECT and low-dose IR strategies.