A Series of Non-Oxido V^IVComplexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity

Abstract

A series of mononuclear non-oxido vanadium(IV) complexes, [VIV(L1–4)2] (1–4), featuring tridentate bi-negative ONS chelating S-alkyl/aryl-substituted dithiocarbazate ligands H2L1–4, are reported. All the synthesized non-oxido VIV compounds are characterized by elemental analysis, spectroscopy (IR, UV–vis, and EPR), ESI-MS, as well as electrochemical techniques (cyclic voltammetry). Single-crystal X-ray diffraction studies of 1–3 reveal that the mononuclear non-oxido VIV complexes show distorted octahedral (1 and 2) or trigonal prismatic (3) arrangement around the non-oxido VIV center. EPR and DFT data indicate the coexistence of mer and fac isomers in solution, and ESI-MS results suggest a partial oxidation of [VIV(L1–4)2] to [VV(L1–4)2]+ and [VVO2(L1–4)]−; therefore, all these three complexes are plausible active species. Complexes 1–4 interact with bovine serum albumin (BSA) with a moderate binding affinity, and docking calculations reveal non-covalent interactions with different regions of BSA, particularly with Tyr, Lys, Arg, and Thr residues. In vitro cytotoxic activity of all complexes is assayed against the HT-29 (colon cancer) and HeLa (cervical cancer) cells and compared with the NIH-3T3 (mouse embryonic fibroblast) normal cell line by MTT assay and DAPI staining. The results suggest that complexes 1–4 are cytotoxic in nature and induce cell death in the cancer cell lines by apoptosis and that a mixture of VIV, VV, and VVO2 species could be responsible for the biological activity.

Halogenated non-innocent vanadium(v) Schiff base complexes: chemical and anti-proliferative properties

“…3–6 Non-innocent Schiff base vanadium-catecholates (V-catecholates) have interesting electronic properties with the potential for redox taking place not only on the metal center but also on the ligand. 3,7–9 The subclass of non-innocent Schiff base V-catecholates have recently been discovered to have desirable pharmaceutical properties 3–6,8–16 which has expanded the knowledge on anti-diabetic and anti-cancer properties of vanadium complexes. 3,4,6,8–18 The reported antiproliferative properties of the class of non-innocent Schiff base V-catecholates were reported to surpass the efficacy of cisplatin in human chondrosarcoma (SW1353) bone cells, T98G glioblastoma cells, aggressive mesenchymal-like MDA-MB-231 cells, A549 (lung) and PANC-1 (pancreas) cancer cell lines, and HFF-1 (human foreskin fibroblasts) normal cells.…”

“…3,7–9 The subclass of non-innocent Schiff base V-catecholates have recently been discovered to have desirable pharmaceutical properties 3–6,8–16 which has expanded the knowledge on anti-diabetic and anti-cancer properties of vanadium complexes. 3,4,6,8–18 The reported antiproliferative properties of the class of non-innocent Schiff base V-catecholates were reported to surpass the efficacy of cisplatin in human chondrosarcoma (SW1353) bone cells, T98G glioblastoma cells, aggressive mesenchymal-like MDA-MB-231 cells, A549 (lung) and PANC-1 (pancreas) cancer cell lines, and HFF-1 (human foreskin fibroblasts) normal cells. The efficacy of these molecules elicited proposals for intratumoral injections 19 as a viable treatment because their potential properties enable intact complexes for cellular uptake which then hydrolyze over time into much less toxic components.…”

Hydrolytically Stable TiIV–Hydrazone-Based Metallodrugs: Protein Interaction and Anticancer Potential

“…Gathering the knowledge from the above discussion and expertise from our earlier research works on the development of metal-based anticancer agents, ,− herein, a series of new titanium­(IV)-hydrazone-based complexes ( 1 – 3 ) were reported and characterized by different physicochemical techniques. In this study, two units of dianionic tridentate ligands were purposefully implemented with the intention of achieving maximum hydrolytic stability of 1 – 3 in aqueous media.…”