Comparison of In Vitro and In Vivo Biological Screening of Nano‐Palladium (II) and Platinum (II)‐Based Compounds With DFT and Molecular Docking Study

ABSTRACT Within the current challenges in medicinal chemistry, the creation of novel and improved therapeutic agents stands out. 2‐Cyano‐3‐(thiophen‐2‐yl)prop‐2‐enethioamide (CTPTA) ligand was complexed with palladium (II) and platinum (II) ions within the nanoscale with the molecular formula [M (CTPTA)Cl 2 ]. H 2 O. The CTPTA ligand and its complexes were characterized by elemental analysis, UV–Vis spectra, FTIR, mass spectra, TGA, magnetic measurement, and the molar conductance technique. Analysis with a scanning electron microscope (SEM) revealed that the nanostructure dimension of both complexes is predominantly between 10 and 30 nm. The CTPTA ligand functions as a bidentate ligand, utilizing thione sulfur, and cyanide nitrogen atoms. Density functional theory was employed to analyze the geometric structure properties of the CTPTA ligand and its complexes. Natural population (NPA) and Mulliken population (MPA) methods were used to calculate the charge distribution. The cytotoxic impact results of all compounds on human liver cancer (HepG2) cell line were satisfactory. The ligand and its complexes were also tested against gram‐negative and gram‐positive bacteria in vitro. The findings of the molecular docking study supported the cytotoxicity and antibacterial effects. The antioxidant and anti‐inflammation activities of synthesized palladium (II) and platinum (II) complexes had a great spectrum of activity. The preclinical pharmacokinetic studies on albino rats revealed that the newly studied complexes achieved excellent antitumor results. This was clear in the investigated parameters, especially the amelioration of AFP levels, liver weight, oxidative stress, and lobular hepatic architecture injury.