Spectral and molecular docking studies of nucleic acids/protein binding interactions of a novel organometallic palladium (II) complex containing bioactive PTA ligands: Its synthesis,anticancer effects and encapsulation in albumin nanoparticles |
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Authors: | Zohreh Mehri Lighvan Hossein Ali Khonakdar Abolfazl Heydari Mina Rafiee Maryam Dehdashti Jahromi Ali Derakhshani Amir Abbas Momtazi-Borojeni |
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Affiliation: | 1. Department of Polymer Processing, Iran Polymer and Petrochemical Institute, P.O. Box 14965-115, Tehran, Iran;2. Polymer Institute of the Slovak Academy of Sciences, Dúbravská cesta 9, Bratislava, 845 41 Slovakia;3. Department of Chemistry, Isfahan University of Technology, Isfahan, 84156/83111 Iran;4. Faculty of Engineering, Jahrom University, Jahrom, Iran;5. Hydatid Desies Center, Kerman Medical University, Kerman, Iran;6. Department of Biotechnology School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran |
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Abstract: | The organometallic palladium complex with nitrogen-containing heterocycles is a potent antitumor agent. Coordination of phosphorus ligands to organometallic complexes increases their hydrophilicity, promotes ligand−DNA interactions and damage level to cancer cells, and blocks division in target cells. In this study, a phosphaadamantane palladium complex ([Pd{(C,N)- (C12H8NH2)} (PTA) Cl], PTA = 1,3,5-Triaza-7-phosphaadamantane) ( 2 ) was synthesized via the reaction of biologically active PTA with binuclear palladacycles [Pd2{(C,N)-(C12H8NH2)}2(μ-Cl)2] ( 1 ). In vitro studies of the complex with DNA (calf-thymus) explored by UV–Vis, emission titration, circular dichroism and helix melting methods showed that the complex interacts with DNA via an intercalative mechanism. Furthermore, competitive binding studies using warfarin, digoxin and ibuprofen site markers containing definite binding sites revealed the binding of the complex to site I on bovine serum albumin. The in vitro release mechanism of the palladium complex exhibited a biphasic pattern characterized by an initial burst release followed by a slower sustained release. Ultimately, in vitro evaluation of cytotoxicity and cell death showed that the complexes were able to decrease the viability of human cancer cell lines (MCF-7 and Jurkat) in a dose-dependent manner, but lower decreases were observed in the viability of normal fibroblast cells ASF-4 at the dosages evaluated. Finally, the order of in vitro anticancer activities was found to be consistent with the DNA-binding affinities. |
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Keywords: | albumin nanoparticle BSA binding DNA binding palladium complex site markers |
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