New anticancer Pt and Pd complexes with binicotinic acid and oxalate derivatives as ligands: Synthesis, cytotoxicity, binding mode on DNA and HSA and molecular docking

• Published in: Inorganica Chimica Acta 2024-11, Vol.572, p.122285, Article 122285
• Main Authors: Eslami Moghadam, Mahboube, Jafari, Ameneh, Shokrollahi, Sodabeh
• Format: Article
• Language: English
• Subjects: Anticancer Pt/Pd complexes; Carboplatin; DNA-binding; Docking simulation; Groove binding; Oxaliplatin
• ISSN: 0020-1693
• DOI: 10.1016/j.ica.2024.122285

[Display omitted] •Some Pt and Pd complexes were synthesized.•The mode of DNA binding was investigated by molecular docking simulation.•Pt/Pd complex-DNA interaction has been studied using spectroscopic methods.•Cytotoxic activities were obtained against several cancerous and normal cell lines. In this project, four new palladium (II) and platinum (II) complexes were designed and prepared to improve metallo-drugs activity in DNA binding and inhibiting cancerous cells. The complexes, 1: [Pt(bpdca)OX], 2: [Pd(bpdca)OX], 3: [Pt(bpdca)(CBDC)], and 4: [Pd(bpdca)(CBDC)] (where bpdca is 2,2′bipyridine-3,3′-dicarboxylic acid, CBDC is cis-1,1′-cyclobutyl dicarboxylato, and OX is oxalate), were structurally specified using experimental and computational analysis. Density functional theory calculations were done to evaluate the structure–activity relationship of these compounds. Also, the cytotoxicity of them was investigated on the human colorectal carcinoma (HCT116), MCF7 (breast cancer), A549 (Human Caucasian lung carcinoma), and HFF (Human Freskin Fibroblast) cell lines. According to the findings, 3 and 4 were more active than oxaliplatin and carboplatin. Because of the CBDC ligand in the designed compound, IC50 values were obtained less than other derivatives against all mentioned cancerous cell lines. Also, regarding IC50 values on normal HFF cell line, 4 is selectively toxic against the A549 cancer cell line with SI = 5.6. Electronic absorption, fluorescence, and CD monitoring were used to follow the binding abilities of all complexes to CT-DNA and HSA. The results indicated that they could interact with CT-DNA through groove mode and with HSA via hydrogen bond and van der Waals forces. Spectral data showed that complexes changed the way the HSA folded by modifying the proportion of a-helix. The metal complex binding with both mentioned biomolecules was predicted using docking simulation, which also verified the groove binding for the DNA-complex. The findings indicated that complex 4 had a greater negative docking energy and a higher propensity for CT-DNA and HSA interaction. So, all complexes can be suitable candidates as anticancer drugs.