Structural, DNA/BSA binding interactions and cytotoxicity studies of carboxamide (pyridyl)pyrazine palladium(II) complexes

• Four mononuclear and dinuclear carboxamide Pd complexes isolated • Molecular structures confirmed using single crystal X-ray analyses • Interactions of the Pd complexes with CT-DNA) investigated. • BSA interactions studies established static quenching mechanism. • Cytotoxic effects of the complexes examined in three cancer cell lines Abstract : Reactions of ligands [ N 2 , N 3 -bis(pyridin-2-yl)pyrazine-2,3-dicarboxamide] ( L1 ), [ N 2 , N 3 -bis(6-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] ( L2 ), [ N 2 , N 3 -bis(4-methylpyridin-2-yl)pyrazine-2,3-dicarboxamide] ( L3 ) and [ N 2 , N 3 -bis(quinoline-8-yl)pyrazine-2,3-dicarboxamide] ( L4 ) with [PdCl 2 (NC Me ) 2 ] afforded the respective palladium(II) complexes: [Pd 2 ( L1 ) 2 Cl 2 ] (Pd1) , [Pd 2 ( L2 ) 2 Cl 2 ] (Pd2) , [Pd 2 ( L3 ) 2 Cl 2 ] (Pd3) and [Pd( L4) Cl] (Pd4) . Molecular structures of complexes Pd1 and Pd3 are dinuclear containing two bridging bidentate ligand units. The interactions of the palladium complexes ( Pd1 - Pd4 ) with calf thymus DNA (CT-DNA) were monitored using UV-Vis and fluorescence spectroscopy and revealed intercalative binding modes, with an intrinsic binding constant (K b ) values in the order of 10 6 M −1 . Bovine serum albumin (BSA) interaction was evaluated using fluorescence techniques and displayed a static quenching mechanism. The cytotoxic effects of the complexes Pd1-Pd4 were examined against human breast cancer cell lines MCF-7 and MDA-MB-231, and human transformed lung cell line MRC5-SV2 (a model of lung cancer) and its parental normal lung fibroblast cell line MRC5. While the complexes Pd1 and Pd4 showed significant to moderate cytotoxicity against MCF-7 (IC 50 of 11.2 µM and 61.5 µM, respectively), complexes Pd2 and Pd3 were inactive. All the complexes were inactive against the MDA-MB-231 cell line, and Pd2-Pd4 were inactive against the MRC5-SV2 cell line. Compounds Pd1 exhibited lower cytotoxicity against the normal cell line MRC5.