Inhibitory activities and possible anticancer targets of Ru(II)-based complexes using computational docking method

2013

Molecules

In cancer chemotherapy, metal-based complexes have been recognized as the most promising means of inhibiting cancer growth due to the successful application of cis-platin and its derivatives above many of the existing organic anticancer agents. The limitations in their rational design can be traced to the complexity of the mechanism of their operations, lack of proper knowledge of their targets and lack of force fields in docking packages to appropriately define the metal centre of the organometallic complexes. In this paper, some of the promising anticancer complexes of Ru(II) such as the rapta-based complexes formulated as [Ru(η6-p-cymene)L2(pta)] and those with unusual ligands are considered. CatB and kinases which have been experimentally confirmed as possible targets of the complexes are also predicted by the three methods as one of the most targeted receptors while TopII and HDAC7 are predicted by two and one of the methods as best targets. The interesting features of the binding of the complexes show that some of the complexes preferentially target specific macromolecules than the others, which is an indication of their specificity and possibility of their therapeutic combination without severe side effects that may come from competition for the same target. Also, introduction of unusual ligands is found to significantly improve the activities of most of the complexes studied. Strong correlations are observed for the predicted binding sites and the orientation of the complexes within the binding site by the three methods of docking. However there are disparities in the ranking of the complexes by the three method of docking, especially that of Glide.

Section: Introductionmentioning

confidence: 99%

Comparing the Suitability of Autodock, Gold and Glide for the Docking and Predicting the Possible Targets of Ru(II)-Based Complexes as Anticancer Agents

2013

Molecules

“…Although results from clinical trials have shown that Ru compounds may be less toxic and more effective and could possibly be alternatives to platinum-based compounds, at present, more research still needs to be done to understand the modes of action of all lead Ru compounds. Our group has been making efforts to predict the possible targets of metal-based complexes as anticancer agents using theoretical docking methods (Adeniyi and Ajibade 2012, 2013a,b,c,d,e, 2014a,b, 2015. However, unlike the organic counterparts, there are very serious limitations in making use of docking tools for metal complexes mainly due to a lack of proper force fields to take care of the metal center (Zhao and Lin 2005).…”

Section: Resultsmentioning

confidence: 99%

Development of ruthenium-based complexes as anticancer agents: toward a rational design of alternative receptor targets

Reviews in Inorganic Chemistry

2016

Self Cite

AbstractIn the search for novel anticancer agents, the development of metal-based complexes that could serve as alternatives to cisplatin and its derivatives has received considerable attention in recent years. This becomes necessary because, at present, cisplatin and its derivatives are the only coordination complexes being used as anticancer agents in spite of inherent serious side effects and their limitation against metastasized platinum-resistant cancer cells. Although many metal ions have been considered as possible alternatives to cisplatin, the most promising are ruthenium (Ru) complexes and two Ru compounds, KP1019 and NAMI-A, which are currently in phase II clinical trials. The major obstacle against the rational design of these compounds is the fact that their mode of action in relation to their therapeutic activities and selectivity is not fully understood. There is an urgent need to develop novel metal-based anticancer agents, especially Ru-based compounds, with known mechanism of actions, probable targets, and pharmacodynamic activity. In this paper, we review the current efforts in developing metal-based anticancer agents based on promising Ru complexes and the development of compounds targeting receptors and then examine the future prospects.

“…The complexes used in this work are designed to play a dual role as anticancer and nonlinear optical (NLO) materials. Docking study of some of these complexes has been found to be promising than many of the RAPTA complexes [31]. The most widely screened ruthenium complexes as anticancer are the halfsandwich complexes [2,3,[32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

The Spectroscopic and Conductive Properties of Ru(II) Complexes with Potential Anticancer Properties

Journal of Spectroscopy

2014

Self Cite

Different density functional methods (DFT) have been used to optimize and study the chemistry of five potential anticancer complexes in terms of their electronic, conductive, and spectroscopic properties. Many of the computed properties in addition to the IR and QTAIM analysis of the NMR are dipole moment vector ( ), linear polarizability tensor ( ), first hyperpolarizability tensors ( ), polarizability exaltation index (Γ), and chemical hardness ( ) of the complexes. Stable low energy geometries are obtained using basis set with effective core potential (ECP) approximation but, in the computation of atomic or molecular properties, the metal Ru atom is better treated with higher all electron basis set like DGDZVP. The spectroscopic features like the IR of the metal-ligand bonds and the isotropic NMR shielding tensor of the coordinated atoms are significantly influenced by the chemical environment of the participating atoms. The carboxylic and pyrazole units are found to significantly enhance the polarizabilities and hyperpolarizabilities of the complexes while the chloride only improves the polarity of the complexes. Fermi contacts (FC) have the highest effect followed by the PSO among all the four Ramsey terms which defined the total spin-spin coupling constant J (HZ) of these complexes.