DNA binding, molecular docking study and antitumor activity of [PdCl<inf>2</inf>(R<inf>2</inf>-(S,S)-eddtrp)] complexes

Abstract

The cytotoxic activity of ligands (O,O′-dialkyl esters of S,S-ethylenediamine-N,N'-di-(3,3′-1H-indol-3yl)propionic acid dihydrochloride (alkyl = ethyl, propyl, butyl, pentyl) and corresponding palladium(II) complexes were determined against human and murine colorectal cancer cells (HCT116 and CT26) and compared to the activities of cisplatin. All tested compounds showed a dose-dependent cytotoxic activity toward used cell lines. According to IC50 values for cytotoxic activities of tested compounds, complex of Pd(II) ion with O,O′-diethyl ester of S,S-ethylenediamine-N,N'-di-(3,3′-1H-indol-3yl) propionic acid dihydrochloride showed significantly, six times higher cytotoxic activity against HC116 cell line, than cisplatin. The interactions of the complexes with calf thymus DNA were analyzed by absorption and emission spectral studies (ethidium bromide displacement studies). The high values of DNA-binding constants (Kb) indicate the good binding affinity for all investigated complexes toward DNA. During the examination of competitive reactions with ethidium bromide, the results showed that complexes can replace ethidium bromide bound DNA and interact with DNA. The molecular docking simulations were applied for better understanding of inhibitory activity of palladium(II) complexes. The obtained values of free binding energies and constants of inhibition also show that the complex of Pd(II) ion with O,O′-diethyl ester of S,S-ethylenediamine-N,N'-di-(3,3′-1H-indol-3yl)propionic acid dihydrochloride has the best inhibitory effect on DNA molecules. Graphic abstract: [Figure not available: see fulltext.].