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

Molecules

Adebayo A. Adeniyi¹ 

[1] id="af1-molecules-18-10829">Department of Chemistry, University of Fort Hare, Private Bag X1314, Alice 5700, South Afri

关键词: ruthenium complexes;    anticancer;    docking methods;    receptors;   

DOI  :  10.3390/molecules180910829

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.