Synthesis, characterization and tumor inhibitory activity of a novel Pd(ii) complex derived from methanethiol-bridged (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-6-yl)(phenyl)methanone

• Published in: New journal of chemistry 2019, Vol.43 (2), p.79-86
• Main Authors: Bodke, Yadav D, Malojirao, Vikas H, , Kandagalla, Shivananda
• Format: Article
• Language: English
• Subjects: Antiangiogenics; Anticancer properties; Apoptosis; Binding; Coordination compounds; Deoxyribonucleic acid; DNA; In vivo methods and tests; Infrared spectroscopy; Ligands; Molecular docking; NMR; Nuclear magnetic resonance; Palladium; Proteins; Survivability; Tumors
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c8nj03057j

In this study, we designed a therapeutic active Pd( ii ) complex with the new (2-((1 H -benzo[ d ]imidazol-2-yl)methylthio)-1 H -benzo[ d ]imidazol-5-yl)(phenyl)methanone ligand in good yield. The structure of the ligand and its Pd( ii ) complex was characterized via IR, UV-visible, 1 H-NMR, 13 C-NMR, mass spectroscopy, TGA and powder XRD techniques. The spectral data of the Pd( ii ) complex indicated the bidentate bonding mode for bis-benzimidazole and suggested a tetrahedral geometry for the metal complex. The in vitro antiproliferative effect of the BIPM ligand and Pd( ii ) complex were tested against the MCF7, A549, Ehrlich ascites carcinoma (EAC) and Daltons lymphoma ascites (DLA) carcinoma cell lines. The metal complex exhibited excellent antiproliferative potency with a significant IC 50 value of ∼10 μm against the EAC cell line compared to the ligand alone with a value of ∼17 μM. Further, the in vivo antitumor effect study on the Pd( ii ) complex against a murine EAC tumor model system showed obvious extended survivability. The tumor inhibitory mechanism of the Pd( ii ) complex is due to its antiangiogenic effect and promotion of apoptosis, as verified by DNA condensation and FACS analysis. The potential photo-induced binding mode on double-stranded calf thymus DNA and protein cleavage activity study on pBR322 DNA of the complex confirmed its apoptotic characteristics. The significant hypochromic shift due to the strong π-π stacking interaction between the metal complex and the base pairs of DNA was clearly shown by the intrinsic DNA binding constant, k b . The molecular docking study on the Pd( ii ) complex interaction with DNA further confirmed its inhibition ability. The experimental results and drug-likeness properties of the Pd( ii ) complex suggest its potential applications, which can be developed as a potent anticancer drug in the near future. This manuscript demonstrates the synthesis and tumor inhibitory activity of (2-((1 H -benzo[ d ]imidazol-2-yl)methylthio)-1 H -benzo[ d ]imidazol-6-yl)(phenyl)methanone and its Pd( ii ) complex.