Novel ternary Pd(II) complexes as potent anticancer drugs for ovarian carcinoma treatment

Abstract

A novel straightforward method has been introduced to synthesize two new water soluble Pd complexes, [Pd(phd)(AA)]NO3, (phd = 1,10-phenanthroline-5,6-dione; 1, AA = L-isoleucine and 2, AA = L-leucine) using water as a green solvent. Complexes 1 and 2 have been characterized by elemental analysis, FT-IR, 1H NMR spectroscopy and mass spectrometry. A theoretical study of these complexes was conducted using ADME, DFT, and molecular docking. ADME data revealed these complexes as potentially anti-cancer drugs. Fluorescence, UV–Vis, and CD spectroscopy were applied to study the mechanism of DNA interaction. As a result of the fluorescence data, both complexes statically quenched DNA. Based on thermodynamic parameters, Pd(II) complexes and DNA interact via an electrostatic approach and groove binding. CD spectra indicated that both complexes exhibit a slight blue shift with a decrease in intensity across all bands. The experimental data were in agreement with DFT calculations and docking studies. In sum, the mode of binding with DNA intracellular structure is via groove binding and electrostatic interactions. Cytotoxic screening of these compounds carried out against the human ovarian carcinoma cell line A2780SP and cisplatin-resistant variant A2780CP revealed that both complexes showed significantly higher anticancer activity against A2780CP cancer cell line compared to cisplatin. Moreover, all theoretical and experimental data show that complex 2 is more active than complex 1.