An Insight into the Anticancer Activities of Ru(II)-Based Metallocompounds Using Docking Methods

Abstract

Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II) complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

A comparative antimicrobial and toxicological study of gold(iii) and silver(i) complexes with aromatic nitrogen-containing heterocycles: synergistic activity and improved selectivity index of Au(iii)/Ag(i) complexes mixture

“…86 MVD has been successfully applied in the docking studies of silver(I) and gold(III) complexes in DNA. 87,88 Hydrogen bonds, hydrophilic and hydrophobic interactions between gold(III) and silver(I) complexes and DNA were calculated. The binding site was computed with a grid resolution of 0.3 Å.…”

Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation

“…Standard procedures were followed during the docking process, as described in Refs. [ [23] , [24] , [25] ].…”

Editorial of Special Issue Ruthenium Complex: The Expanding Chemistry of the Ruthenium Complexes

“…That interest in the bioactivity profiles of ruthenium complexes has grown rapidly is amply demonstrated by design of new Ru compounds inhibiting enzymes, by the novel multinuclear systems acting as drug delivery vehicles or imaging and theranostics agents and signal transduction elements. A major contribution came as well from the advent of refined bioanalytical, biophysical and spectroscopic techniques used to elucidate the structure and the in vivo functioning of these complexes [79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100]. Some arene-functionalized dinuclear organometallic Ru(II) complexes are capable of crosslinking model peptide and oligonucleotide sequences while cytotoxicities are linked to their more rigid or more flexible conformations [81].…”