Exploring the antitumor effects of Pd(II) complexes with nitrogen donor ligands towards breast carcinoma

Pd(II)-containing complexes exhibit considerable potential as therapeutic agents against cancer owing to their proficiency in selectively targeting neoplastic cells compared to cisplatin. In this context, we describe the synthesis of square planar palladium complexes of the general formula [Pd(L¹⁻⁸)₂] from imino-amido-based asymmetrical (NN) proligands (HL¹⁻⁸) and characterized based on melting point, CHN analysis, spectroscopic techniques (FT-IR, ¹H NMR, ¹³C NMR), and ESI–MS. DFT computations are employed to elucidate the characteristics of the frontier orbitals and MEP analysis. In the current investigation, the precursors, proligands, Pd(II) complexes and cisplatin were systematically assessed for their anticancer efficacy against breast carcinoma (BT-474, BT-483, and BT-459) by MTT assay. Among the compounds subjected to evaluation, the complex [Pd(L⁷)₂] demonstrated superior capacity in inhibiting the proliferation of breast cancer cells, exhibiting median inhibitory concentration (IC₅₀) values of 6.10, 9.01, and 7.20 µM than standard cisplatin (IC₅₀ = 18.70, 19.40, 19.30 µM), respectively. Cellular apoptosis assessment of [Pd(L⁵⁻⁸)₂] exhibited characteristic apoptotic phenomena including membrane blebbing and DNA condensation. Furthermore, electronic spectroscopy was used to evaluate the binding modalities of complexes with CT DNA, supported by the in silico docking studies. [Pd(L⁷)₂] exhibited the mixed binding mode with a binding affinity in the range of 10⁴ M⁻¹.