Exploring Anticancer Activities and Structure–Activity Relationships of Binuclear Oxidovanadium(IV) Complexes

Abstract

Dimeric mixed-ligand oxidovanadium complexes [V2O2(1,3-pdta)­(bpy)2]·9H2O (1) and [V2O2(1,3-pdta)­(phen)2]·6H2O (2) feature a symmetric binuclear structure bridged by 1,3-pdta, which is different from our previous reported asymmetric binuclear complex [V2O2(edta)­(phen)2]·11H2O (3).In this study, a wide range of analytical techniques were carried out to fully characterize the complexes 1 and 2 and further investigate their structural stabilities. Density functional theory calculations of 1 and 2 also suggest that they might have good reactivity with biomolecules as anticancer agents. To assess and screen the antitumor activities of compounds 1–3 together with their four corresponding monomeric complexes [VO­(ida)­(phen)], [VO­(ida)­(bpy)], [VO­(OH)­(phen)2]­Cl, and [VO­(Hedta)]−, we have performed in vitro experiments with hepatocellular carcinoma HepG2 and SMMC-7721 cell lines by MTT analyses. Complex 2 was found to have the highest inhibitory potency against the growth of HepG2 and SMMC-7721 cells (IC50 = 2.07 ± 0.72 μM for HepG2; 13.00 ± 3.06 μM for SMMC-7721) compared to other compounds. The structure–activity relationship studies showed that the antitumor effect of compound 2 is higher than that of other compounds. After studying the monomeric compounds of 1–3, their effects were also ranked. Moreover, complex 2 displayed stronger binding affinity toward calf thymus DNA (K b = 5.71 × 104 M–1) and cleavage activities than the other complexes (K b = 1.34 × 104 M–1 for 1 and 5.22 × 104 M–1 for 3, respectively). We further extended the cellular mechanisms of drug action and found that 2 could block DNA synthesis and cell division of HepG2 and 7721 cells and further induce apoptosis by flow cytometry assays. In short, these results indicate that binuclear oxidovanadium compounds could have potential as simple, effective, and safe antitumor agents.

Synthesis, In Vitro, and Computational Studies of PTP1B Phosphatase Inhibitors Based on Oxovanadium(IV) and Dioxovanadium(V) Complexes

“…Because vanadate has a structural similarity to phosphate, it has been proposed as a phosphate transition state analog in phosphatases. Therefore, vanadium compounds are of great interest as antidiabetic agents and, more recently, as potential anticancer drugs [32][33][34].…”

A Keggin-type polyoxomolybdate-based crystalline material formed by hydrothermal transformation: photo/electro-catalytic properties and mechanism study

“…Polyoxometalates (POMs), which are well-known nanoscale metal-oxo clusters, have gained keen interest in the fields of photo/electro-catalysis, 1–8 pharmacy, 9,10 magnetism and medicinal chemistry, 11–14 due to their accurate and diverse molecular structure, concise preparation, semiconductor-like features, reversible redox capacity and other charming properties. 15–18 However, the good solubility of POM compounds in an aqueous solution greatly reduces the recovery accessibility and cyclic stability, which limits their practical application in many fields to a certain extent.…”