Catalase inhibition by two Schiff base derivatives. Kinetics, thermodynamic and molecular docking studies

Abstract

Cisplatin and its derivatives, because of their success in treating cancer, continue to be of interest to researchers and an incentive for them to synthesize new transition metal complexes. So, we have explored the effects of two potential anticancer metal complexes which have different metal centers on the function and structure of bovine liver catalase (BLC) by spectroscopic and molecular docking simulation. Kinetics results showed both complexes inhibited BLC through a mixed-type inhibitory mechanism. The molecular docking study in the well coherent with kinetics results confirmed that Pd and Zn complexes did not directly bind into the catalase activity site, but the binding of them into the enzyme cavity influenced the microenvironment of the BLC activity site which resulted in the reduced BLC activity. Results obtained from UV–Vis, circular dichroism (CD) and synchronous fluorescence showed that the structure and conformation of BLC were altered by Zn (II) and Pd(II) complexes. Both complexes changed the secondary structure of BLC by decreasing α-helix and increasing β-sheet content. According to binding constant values (K300 K = 6.31 ± 2.67 × 105 M−1, K310 K = 0.89 ± 0.09 × 105 M−1 for Zn complex and K300 K = 0.40 ± 0.03 × 105 M−1, K310 K = 0.19 ± 0.02 × 105 M−1 for Pd complex), they quenched the intrinsic fluorescence of BLC via a static mechanism. Thermodynamic parameters in agreement with molecular docking results demonstrated that Schiff base complexes could combine with BLC spontaneously through hydrogen bonds and Van der Waals forces. The results of the molecular docking calculations show that the best binding site of both complexes on BLC is located at a cavity among the wrapping domain, N-Terminal arm and β-barrel. All of these results show the relative similarities of zinc and palladium complexes in biological interactions and provides experimental evidence for better understanding the activity mechanism of different anticancer drugs.