Effect of N-substituted aliphatic glycine presence on bioactivity, cytotoxicity, and selectivity of Pt(II) and Pd(II) complexes in cancer treatment

Abstract

In this study, four new platinum (II) and palladium(II) complexes were synthesized to develop metallo-drugs that can attach to DNA and prevent the division of cancer cells. The complexes, 1: [Pt(bipy)(LP)]NO3, 2: [Pt(bipy)(LA)]NO3, 3: [Pd(bipy)(LP)]NO3, and 4: [Pd(phen)(LP)]NO3 (where LP is propylglycine, LA is 2-heptyl glycine, bipy is 2,2-bipyridine, and phen is 1,10-phenanthroline), were structurally characterized using computational and experimental analysis. Their stability, solubility, and lipophilicity were evaluated. Single-crystal X-ray and powder X-ray crystallographic analyses were performed for [Pt(bipy)(LA)]NO3. Density functional theory calculations were performed to investigate the reactivity, stability descriptors, and natural bond orbital analysis of these complexes. The in vitro cytotoxicity of these substances was examined against the human colorectal carcinoma (HCT116), A549 (Human Caucasian lung carcinoma), MCF7 (breast cancer), and HFF (Human Freskin Fibroblast) cell lines. According to the findings, complexes 4 and 3 had near oxaliplatin concentrations and more than carboplatin due to lipophilic ligands in their structure. Also, regarding IC50 values on normal HFF cell line, 4 is selectively toxic against the A549 cancer cell line with SI=5.6. Fluorescence, electronic absorption spectroscopy, and CD spectroscopy were used to investigate the binding affinities of compounds to CT-DNA and HSA. The results revealed that they could interact with CT-DNA through groove mode and with HSA via hydrogen bond and van der Waals forces. Electronic absorption and CD spectra indicated that compounds changed the way the HSA folded by increasing the proportion of a-helix. The binding posture of the metal complex to both biomolecules was predicted using docking simulation, which also verified the groove binding for DNA-complex. The findings indicated that complex 4 had a greater negative docking energy and a higher propensity for CT-DNA and HSA interaction.