Pd(II) based anticancer drug candidates with 1,2-Aminoethyl piperidine scaffold and sulfur donor ancillary: Their in vitro bio-activity, molecular docking and DFT study

Abstract

A series of Pd(II) complexes Pd-1 to Pd-6; out of these [Pd(PIEAM)(LC)]+; Pd-3, [Pd(PIEAM)(NALC)]; Pd-4, [Pd(PIEAM)(GSH)]; Pd-5 and [Pd(PIEAM)(DL-meth)]2+; Pd-6 have been synthesized from water soluble stable diaqua complex [Pd(PIEAM)(OH2)2](NO3)2; Pd-2. The Pd-2 complex was obtained from hydrolysis of [Pd(PIEAM)Cl2]; Pd-1 (where, PIEAM = 1,2-Aminoethyl piperidine, a bidentate carrier ligand and with ancillary groups like; LC = L-cysteine, NALC = N-acetyl-L-cysteine, GSH = Glutathione, DL-meth = DL-methionine). All these Pd-1-Pd-6 complexes were characterized by different spectroscopic studies, like; UV–Vis, FT-IR, 1H NMR, and ESI Mass analyses. The bioactivity and drug-likeness properties of the complexes were assessed by PASS and ADME prediction software. The bioactivity of the complexes was experimentally investigated on DNA binding properties by gel electrophoresis, electronic, fluorescence, and viscometric methods. The binding constant values of Pd-3 complex with CT DNA bining in both absorption (Kb = 7.50 × 104M−1)and fluorosence titration (KSV = 35.10 × 103 M−1) was found greater than other Pd-1, Pd-2, Pd-4-Pd-6 complexes (Kb = (4.25–0.64) × 104 M−1; KSV = (13.57–1.11) × 103 M−1). The comparison in BSA bining of Pd(II) complexes also suggested the higher binding constant of Pd-3 complex in both spectroscopic method (Kb = 32 × 103M−1; KSV = 2.32 × 104 M−1) than other Pd(II) complexes (Kb = 16–2.4 × 103M−1; KSV = 1.99–1.53 × 104 M−1). A theoretical investigation of the structural property and TD-DFT of the complexes was executed by DFT calculations. The detailed BSA binding activity of the complexes was performed by fluorescence quenching, synchronous, and 3D-fluorescence spectroscopic methods. Molecular docking of the complexes with DNA and BSA was under study for their binding mode and different weak forces. Their cytotoxic behaviors, like; anticancer activity by MTT assay and ROS (Reactive Oxygen Species) generation by NBT (Nitro Blue Tetrazolium) assay, were investigated. The cytotoxicity of the complexes was under investigation on human lung adenocarcinoma cell A549, colorectal carcinoma cell HCT 116, and normal human embryonic kidney cell HEK 293.