Cyclopalladated complexes containing metformin and benzylamine derivatives: Synthesis, characterization, binding interactions with DNA and BSA, in vitro cytotoxicity studies

Abstract

A metformin containing palladium complex, [Pd(Met)2](OAc)2 (1), and several cyclopalladated complexes of the general formula [Pd(benzylamine)(Met)](NO3), in which Met is metformin drug and benzylamine is dl-α-methylbenzylamine (2), N,N-dimethylbenzylamine (3), N-ethylbenzylamine (4) and N-t-buthylbenzylamine (5), have been synthesized and characterized using elemental analysis, FT-IR and NMR spectroscopy. Spectroscopic titrations, displacement experiments, DNA melting and circular dichroism (CD) spectroscopy have been applied in the investigation of complexes (1), (2) and free metformin, DNA binding properties. The complexes and free metformin bind to CT-DNA (Calf thymus DNA) efficiently through groove binding and intercalation modes, respectively, according to the results obtained. The corresponding intrinsic binding constants, Kb, of the complexes and free metformin are as follows:metformin>complex (2)>complex (1).Strong association of complexes (1), (2) and free metformin with BSA via a static mechanism with intrinsic binding constants (Kb) in 1.18×104–4.81×104M−1 concentration range is indicated by absorption and emission measurements.The binding sites of complexes and free metformin on BSA were located at sites I and II of BSA, respectively, as demonstrated by competitive experiments. The in vitro cytotoxic activities of complexes (1), (2) and free metformin were evaluated against Hela (cervical cancer), MCF7 (breast cancer) and A549 (lung cancer) cellular lines.