Noncovalent interactions of antitumor cycloplatinated complexes containing trifluoroacetate ligands as the leaving group with bovine serum albumin. Implications for drug design

• Published in: New journal of chemistry 2023-07, Vol.47 (27), p.1292-12913
• Main Authors: Aseman, Marzieh Dadkhah, Negaresh, Parisa, Shojaeifard, Zahra, Hemmateenejad, Bahram, Nabavizadeh, S. Masoud
• Format: Article
• Language: English
• Subjects: Aqueous solutions; Binding sites; Cancer; Cattle; Emission analysis; Fluorescence; Inductively coupled plasma; Ionic interactions; Ligands; NMR; Nuclear magnetic resonance; Optical emission spectroscopy; Proteins; Quinoline; Serum albumin; Spectrum analysis; Structural analysis; Titration; Toxicity
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d3nj00867c

The biomolecular interactions of two previously reported cycloplatinated complexes, [Pt(C^N)(SMe 2 )(OCOCF 3 )] (C^N = deprotonated benzo[h]quinoline (bhq), 1 , or deprotonated 2-phenylpyridine (ppy), 2 ), with bovine serum albumin (BSA) were investigated using various spectroscopic techniques. Structural characterization of 1 and 2 by NMR, UV-vis spectroscopies and conductivity measurements in aqueous media revealed that the TFAc functions as a leaving group ligand and is rapidly replaced by water molecules to form cationic cycloplatinated complexes having an aqua ligand, [Pt(C^N)(SMe 2 )(H 2 O)] + [CF 3 COO] − . Fluorescence titration of BSA indicated a strong binding interaction between Pt( ii ) compounds and protein with a static quenching mechanism. The thermodynamic parameters (Δ H °, Δ G ° and Δ S °) showed that the binding was exothermic, involving main noncovalent hydrophobic forces and ionic interactions. As revealed by the displacement experiment, while 1 could bind to subdomain IIIA (site II) of albumin, the binding sites of 2 were mostly located at subdomain IIA (site I). The synchronous fluorescence spectra indicate that the cycloplatinated compounds induce structural changes in the protein structure. Moreover, far-UV CD spectroscopy is in agreement with a reduction of the α -helix content of albumin through binding. Further evidence for noncovalent association was obtained from inductively coupled plasma-optical emission spectroscopy (ICP-OES). In addition, the cytotoxicity investigation of 1 as a model complex against two human leukemic cancer cell lines (K562 and HL-60), MCF-7 (human breast adenocarcinoma), U-87MG (human glioblastoma cell line) and HT-29 (human colorectal adenocarcinoma cell line) suggested that 1 is more cytotoxic than cisplatin against HL-60 and generally toxic toward K562, MCF-7 and U-87MG. Finally, the quantitative structure-activity relationship (QSAR) was applied to correlate the structure of some cycloplatinated complexes including 1 and 2 with the SA albumin binding constant. The cytotoxicity and biomolecular interactions of monofunctional cycloplatinated( ii ) complexes, [Pt(C^N)(OCOCF 3 )(SMe 2 )], involving trifluoroacetate ligands as the leaving group are investigated by using different spectrophotometric techniques.