Multi experimental and computational studies for DNA and HSA interaction of new nano-scale ultrasound-assisted synthesized Pd(II) complex as a potent anticancer drug

Abstract

As for daily increasing mortality rate in world due to the growth of cancer causing agents, design and synthesis of new compounds with anticancer potential benefits is one of the most important challenges for researchers. In the present work, we synthesized a new Schiff base Pd(II) complex in bulk-scale and also in nano-scales by Sonochemical method. The structure of synthesized complex was determined by single crystal X-ray diffraction technique. Then the cell viability percent of HeLa cancer cells was studied by MTT assay. The results confirmed that reducing the size has salient effect in annihilation of cancer cells. Also, nano-scale complex reached to IC50 in 10 μM of concentration. Binding ability of the nano- and bulk-scale Pd(II) Schiff base complex with calf thymus DNA and human serum albumin was investigated using combination of experimental (fluorescence, circular dichroism (CD) and viscosity) and computational (molecular docking, molecular dynamics simulation and QM/MM) methods. The estimated binding constants for the complex in both of bulk- and nano-scales showed that the nano-scale complex binds more tightly to DNA than its bulk-scale form. This finding is in good agreement with MTT assay results. Molecular docking studies revealed that Pd(II) complex binds to the minor groove and IB binding site of DNA and HSA, respectively. Also, MD simulation studies showed that complexation with the Pd(II) complex changes the structure of HSA with compared to free protein. Finally, the ONIOM results indicated that the structural parameters of the compound changed along with binding to DNA and HSA, indicating the strong interaction between the compound and these biomacromolecules. The values of binding constants depend on the extent of the resultant changes.