Fast, Facile and Solvent‐Free Dry‐Melt Synthesis of Oxovanadium(IV) Complexes: Simple Design with High Potency towards Cancerous Cells

Zegke, Markus; Spencer, Hannah L. M.; Lord, Rianne M.

doi:10.1002/chem.201902441

Cited by 5 publications

(11 citation statements)

References 88 publications

(135 reference statements)

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“…The preparation procedure of the ligands (HL n ) was described in details by Japp-Klingemann reaction [17,18] between the diazonium salt of aniline derivatives (0.01 mol) and dimedione (1.40 g, 0.01 mol). The solid azo dyes represented in Figure 1, were collected by filtration, washed with water and dried in oven at 80 C. Finally, the compounds were recrystallized from methanol to give colored crystals (HL n ).…”

Section: Synthesis Of the Ligands (Hl N )mentioning

confidence: 99%

Synthesis and structural characterization of oxovanadium(IV) complexes of dimedone derivatives

Al‐Hazmi

Abou‐Melha

Althagafi

et al. 2020

Applied Organom Chemis

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We have successfully synthesized new oxovanadium (IV) complexes with dimedone derivatives and their structure were confirmed by elemental analyses, spectroscopic techniques (FT-IR, UV-visible, EPR) and thermal analysis. The reaction of [VO (acac) 2 ] with the azo dimedone ligands (HL n) produced mononuclear oxovanadium (IV) complexes with formula [VO (L n) 2 ] H 2 O. Results of the molar conductance proved that VO 2+ complexes are nonelectrolytes and fall in the range 14-16 Ω-1 cm 2 mol −1. The coordination geometry of VO (IV) complexes is square-pyramidal, where vanadium (IV) ion is coordinated by oxygen atom of the carbonyl (C=O) group, and nitrogen atom of the deprotonating hydrazone moiety (-NH-), while the fifth position is occupied by an oxo group. Moreover, the optimized structure, bond angles, bond lengths, as well as the calculated quantum chemical parameters of the complexes have been estimated. DNA binding activities of the complexes were investigated using electronic absorption titration and viscosity measurements. The obtained results showed groove binding of the complexes to CT-DNA accompanied with a partial insertion of the ligand between the base stacks of the DNA with a binding constant of 2.07-5.51 x 10 5 M −1 range. Evaluation results of the synthesized complexes against the human cancer cell lines HepG-2 and MCF-7, as compared to the positive controls in the viability assay of vinblastine and colchicine have been reported. The in vitro anti-oxidant activity of all the complexes is determined by DPPH free radical-scavenging assay. Finally, the anti-microbial activities of the complexes have been investigated against fungal (Candida albicans), gram negative bacteria (Escherichia coli), and gram positive bacteria (Staphylococcus aureus) using the discdiffusion method.

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Section: Synthesis Of the Ligands (Hl N )mentioning

confidence: 99%

Synthesis and structural characterization of oxovanadium(IV) complexes of dimedone derivatives

Al‐Hazmi

Abou‐Melha

Althagafi

et al. 2020

Applied Organom Chemis

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“… Packing diagram of compound 6 (DMSO‐adduct) and compound 8 (adduct‐free). Showing the interactions of the vanadyl with neighbouring molecules [32] …”

Section: Resultsmentioning

confidence: 99%

“…The in vitro antiproliferation activity of complexes 1 – 9 was evaluated by the MTT assay at dosages between 0.1–100 μ m , and repeated to confirm our previous cytotoxicity studies on these complexes [32] . Screening was conducted against of two human cancer cell lines, lung (A549) and pancreatic (MIA PaCa‐2), and the normal retinal epithelium (RPE‐1) cell line.…”

Section: Resultsmentioning

confidence: 99%

“…In 2019, we reported a series of bis(β‐diketonato) oxovanadium(IV) complexes ( 1 – 9 ) through a facile and straightforward solid state synthesis, and show the complexes exhibit high cytotoxicity and selectivity towards cancer cells, with IC 50 values up to 11.5× higher than cisplatin [32] . The complexes are also stable under physiological conditions and UV/Vis studies show interaction with BSA (bovine serum albumin).…”

Section: Introductionmentioning

confidence: 99%

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Understanding the Potential In Vitro Modes of Action of Bis(β‐diketonato) Oxovanadium(IV) Complexes

et al. 2021

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To understand the potential in vitro modes of action of bis(β‐diketonato) oxovanadium(IV) complexes, nine compounds of varying functionality have been screened using a range of biological techniques. The antiproliferative activity against a range of cancerous and normal cell lines has been determined, and show these complexes are particularly sensitive against the lung carcinoma cell line, A549. Annexin V (apoptosis) and Caspase‐3/7 assays were studied to confirm these complexes induce programmed cell death. While gel electrophoresis was used to determine DNA cleavage activity and production of reactive oxygen species (ROS), the Comet assay was used to determine induced genomic DNA damage. Additionally, Förster resonance energy transfer (FRET)‐based DNA melting and fluorescent intercalation displacement assays have been used to determine the interaction of the complexes with double strand (DS) DNA and to establish preferential DNA base‐pair binding (AT versus GC).

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“…As previously hypothesised with BMOV 35 , the more oxidising conditions should generate higher cellular levels of the vanadium(V) ion, which is a more effective phosphatase inhibitor 35 , and consequently higher cytotoxicity. Oxidovanadium complexes can have lower cytotoxicity in non-tumour cells compared to tumour cells 35,52,53 and it will be of interest to examine if this relates to these cells' more reducing environment.…”

Section: Discussionmentioning

confidence: 99%

The liposomal delivery of hydrophobic oxidovanadium complexes imparts highly effective cytotoxicity and differentiating capacity in neuroblastoma tumour cells

Irving

Tagalakis

Maeshima

et al. 2020

Sci Rep

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Oxidovanadium complexes with organic ligands are well known to have cytotoxic or differentiating capabilities against a range of cancer cell types. Their limited use in clinical testing though has resulted largely from uncertainties about the long-term toxicities of such complexes, due in part to the speciation to vanadate ions in the circulation. We hypothesised that more highly stable complexes, delivered using liposomes, may provide improved opportunities for oxidovanadium applications against cancer. In this study we sourced specifically hydrophobic forms of oxidovanadium complexes with the explicit aim of demonstrating liposomal encapsulation, bioavailability in cultured neuroblastoma cells, and effective cytotoxic or differentiating activity. Our data show that four ethanol-solubilised complexes with amine bisphenol, aminoalcohol bisphenol or salan ligands are equally or more effective than a previously used complex bis(maltolato)oxovanadium(V) in neuroblastoma cell lines. Moreover, we show that one of these complexes can be stably incorporated into cationic liposomes where it retains very good bioavailability, apparently low speciation and enhanced efficacy compared to ethanol delivery. This study provides the first proof-of-concept that stable, hydrophobic oxidovanadium complexes retain excellent cellular activity when delivered effectively to cancer cells with nanotechnology. This offers the improved prospect of applying oxidovanadium-based drugs in vivo with increased stability and reduced off-target toxicity.

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Fast, Facile and Solvent‐Free Dry‐Melt Synthesis of Oxovanadium(IV) Complexes: Simple Design with High Potency towards Cancerous Cells

Abstract: Figure 3. UV/Vis spectra of A) complex 3 at an initial pH of 6.65 and the spectrum obtained by decreasingt he pH with 0.01-0.1 m HCl and B) complex 3 at an initial pH of 6.59 and the spectrum obtained by increasing the pH with 0.01-0.1 m NaOH.

Cited by 5 publications

References 88 publications

Synthesis and structural characterization of oxovanadium(IV) complexes of dimedone derivatives

Synthesis and structural characterization of oxovanadium(IV) complexes of dimedone derivatives

Understanding the Potential In Vitro Modes of Action of Bis(β‐diketonato) Oxovanadium(IV) Complexes

The liposomal delivery of hydrophobic oxidovanadium complexes imparts highly effective cytotoxicity and differentiating capacity in neuroblastoma tumour cells

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