Metformin Containing Nickel (II) Complexes: Synthesis, Structural Characterization, Binding and Kinetic Interactions with BSA, Antibacterial and in-vitro Cytotoxicity Studies

摘要

In quest of antimicrobial and anticancer agents, metformin containing Ni (II) complexes, [Ni (Met)(2)]ClOH (1) and [Ni (Met)(IDA)] (2) {Met: metformin, IDA: iminodiacetic acid} were synthesized and X-ray structure of 1 is four-coordinate square planar geometry. Bovine serum albumin (BSA) interaction and binding studies to Met, IDA and their Ni (II) complexes were investigated and showed a strong interaction. A static quenching process was proposed at low concentrations of compounds whereas, combined quenching process was observed for 1 and 2 at higher concentrations. Kinetic stability, affinity and association constants of compounds-BSA were studied using stopped-flow technique and a mechanism was proposed: a fast and reversible step of BSA binding including complex formation and dissociation was proposed; for the second step, a reversible reaction was observed for 1 and 2 whereas, an irreversible reaction with Met and IDA was observed indicating that coordination with nickel ions change the interaction mechanism. Additionally, the antibacterial investigation against both Gram-positive and Gram-negative bacteria showed that all compounds exhibited significant activities. They also show cytotoxicity against HepG2 human liver cancer cell but the half maximal inhibitory concentration (IC50) values obtained for the cell lines were higher in comparison with cisplatin. Although Met-BSA and IDA-BSA are kinetically more stable than that of 1-BSA and 2-BSA, 1-BSA and 2-BSA showed better antibacterial and cytotoxic activities which is in agreement with the binding constants.