In Vitro DNA/BSA Binding, Anticancer and Normal Cell Activity of Pd(II) Complexes: Substitution Behaviour and Computational Study. Issue 13 (10th April 2018)

• Record Type: Journal Article
• Authors: Mukherjee, Subhajit; Mitra, Ishani; B., Venkata P. Reddy; Das, Payel; Misini, Bashkim; Linert, Wolfgang; Moi, Sankar Ch.
• Is Part Of: ChemistrySelect. Volume 3:Issue 13(2018)
• Page Start: 3871
• Page End: 3885
• Publication Date: 2018-04-10
• Subjects: Pd(II) complexes -- Cytotoxicity -- DNA binding -- Kinetics -- Density functional theory; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201800211
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: In the aspect of an effective palladium based anticancer drug design, Pd(II) complexes [Pd(MAMP)Cl2 ], C1 ; [Pd(MAMP)(H2 O)2 ]x2, C2 ; [Pd(MAMP)(L‐cys)]x, C3 ; [Pd(MAMP)(N‐ac‐L‐cys)], C4 ; [Pd(MAMP)(DL‐meth)]x2, C5 ; and [Pd(MAMP)(DL‐pen)]x, C6 (where x=ClO4 − /NO3 − ) have been synthesised and characterised where 2‐[(methylamino)methyl]pyridine (MAMP) has been considered as carrier ligand and chloride, aqua, L‐cysteine (L‐cys), N‐acetyl‐L‐cysteine (N‐ac‐L‐cys), DL‐methionine (DL‐meth) and DL‐penicillamine (DL‐pen) are selected as leaving group. DNA as well as protein binding ability of the complexes has been investigated with CT‐DNA and BSA and the related binding parameters have been evaluated. Kinetic investigation for the reactions of Pd(II)‐diaqua complex C2 with four selected sulfur containing bio‐molecules have been carried out under pseudo first order condition. In addition, theoretical investigation has also been considered for structural optimisation, frontier molecular orbital mapping, TD‐DFT and NBO analysis. To get an insight into the cytotoxicity, the complexes have been treated on three different cancer cell lines (A549, HeLa, Hep G2) which reveal comparable anticancer activity of the reported complexes with the clinically acquainted anticancer drug Cisplatin. Very less complex initiated reactive oxygen species (ROS) with low degree of cell death in two different non‐tumour cell lines (L6 myotubes and HEK 293) indicate minimum normal cell toxicity of the complexes. Abstract : Pd(II) complexes with 2‐[(methylamino)methyl]pyridine carrier ligand have been explored with good DNA as well as BSA binding nature. The complexes reveal significant cytotoxicity on lung, liver and cervical cancer cells with reduced toxicity on non‐tumour cells like human embryonic kidney cells and model rat skeletal myoblast cells compared to Cisplatin.