ABSTRACT
To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7 × 103 M-1, 2.65 × 103 M-1, 0.3 × 103 M-1, and 4.4 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 25 °C, respectively. Also, binding constants of 1.9 × 103 M-1, 15.17 × 103 M-1, 1.9 × 103 M-1, and 13.1 × 103 M-1 were determined for Pd(II) and Pt(II) complexes (I-IV) at temperature of 37 °C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer. Communicated by Ramaswamy H. Sarma.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Colorectal Neoplasms/pathology , Molecular Docking Simulation , Organoplatinum Compounds/pharmacology , Serum Albumin, Human/metabolism , Spectrometry, Fluorescence/methods , Binding Sites , Colorectal Neoplasms/drug therapy , Coordination Complexes/chemistry , Coordination Complexes/metabolism , HCT116 Cells , Humans , Molecular Structure , Organoplatinum Compounds/chemistry , Protein Binding , Protein Conformation , Serum Albumin, Human/chemistry , ThermodynamicsABSTRACT
In the present study, the biological activities of a new synthesized Pt(II)-complex, 2,2' bipyridinphenyl isopentylglycin Pt(II) nitrate was investigated via its interaction with the most important blood carrier protein of human serum albumin (HSA), using fluorescence and Far-UV circular dichroism (CD) spectroscopic techniques and also molecular docking. Moreover, cytotoxicity activity of the complex was studied against breast cancer cell line of MDA MB231 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching mechanism. According fluorescence quenching data, the binding parameters of the interaction were calculated and showed that hydrophobic interaction has an important role. The molecular docking results in coherent with fluorescence measurements illustrated that Pt(II) complex can bind to HSA at one position that located in the hydrophobic cavity of groove between drug site I and II. Also, experimental data on driving force in binding site was confirmed whereas theoretical results demonstrated Pt(II) complexinteract to HSA by hydrophobic interaction. Far-UV-CD results showed that Pt(II)-complex induced an increasing in the content of α-helical structure of the protein and stabilized it. Also, MTT assay represented growth inhibitory effect of the complex toward the breast cancer cell line.
