Background
Type: Article

Self-recognition of the racemic ligand in the formation of homochiral dinuclear V(V) complex: In vitro anticancer activity, DNA and HSA interaction

Journal: European Journal of Medicinal Chemistry (02235234)Year: 2017Volume: 135Issue: Pages: 230 - 240
GreenDOI:10.1016/j.ejmech.2017.04.053Language: English

Abstract

The reaction of a racemic mixture of Schiff base tridentate ligand with vanadium(V) affords homochiral vanadium complex, (VO(R-L))2O and (VO(S-L))2O due to ligand “self-recognition” process. The formation of homochiral vanadium complex was confirmed by 1H NMR, 13C NMR and X-ray diffraction. The HSA- and DNA-binding of the resultant complex is assessed by absorption, fluorescence and circular dichroism (CD) spectroscopy methods. Based on the results, the HSA- and DNA-binding constant, Kb, were found to be 8.0 × 104 and 1.9 × 105 M−1, respectively. Interestingly, in vitro cytotoxicity assay revealed the potent anticancer activity of this complex on two prevalent cancer cell lines of MCF-7 (IC50 value of 14 μM) and HeLa (IC50 value of 36 μM), with considerably low toxicity on normal human fibroblast cells. The maximum cell mortality of 12.3% obtained after 48 h incubation of fibroblast cells with 100 μM of the complex. Additionally, the specific DNA- and HSA-binding was also shown using molecular docking method. The synthesized complex displayed high potential for biomedical applications especially for development of novel and efficient anticancer agents. © 2017 Elsevier Masson SAS


Author Keywords

Dinuclear vanadium complexDNA- and HSA-bindingHomochiral metal complexIn vitro assaySelf-recognition

Other Keywords

Antineoplastic AgentsCell ProliferationCell SurvivalDNA, NeoplasmDose-Response Relationship, DrugDrug Screening Assays, AntitumorFibroblastsHeLa CellsHumansLigandsMCF-7 CellsMolecular Docking SimulationOrganometallic CompoundsSerum AlbuminStructure-Activity RelationshipVanadiumantineoplastic agentDNAhuman serum albuminligandmetal complexSchiff baseorganometallic compoundabsorption spectroscopyantineoplastic activityArticlebinding affinitycarbon nuclear magnetic resonancecell deathchiralitycircular dichroismcontrolled studycytotoxicity assaydrug cytotoxicitydrug DNA bindingdrug potencydrug protein bindingfibroblastfluorescence spectroscopyHeLa cell linehumanhuman cellIC50in vitro studyMCF-7 cell linemolecular dockingMTT assayproton nuclear magnetic resonanceracemic mixtureX ray diffractionantagonists and inhibitorschemistrydose responsedrug effectsdrug screeningstructure activity relationsynthesis