Τίτλος:
Unraveling the binding mechanism of an Oxovanadium(IV) – Curcumin complex on albumin, DNA and DNA gyrase by in vitro and in silico studies and evaluation of its hemocompatibility
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
An oxovanadium(IV) – curcumin based complex, viz. [VO(cur)(2,2´-bipy)(H2O)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (Kb) was calculated to be 2.56 x 105 M-1, whereas a single great-affinity binding site was revealed. Moreover, the hemocompatibility test demonstrated that the complex presented low hemolytic fraction (mostly below 1%), in all concentrations tested (0-250 μΜ of complex, 5% DMSO) assuring a safe application in interaction with blood. The binding of the complex to DNA was also investigated using absorption, fluorescence, and viscometry methods indicating a binding through a minor groove mode. From competitive studies with ethidium bromide the apparent binding constant value to DNA was estimated to be 4.82 x 106 M-1. Stern-Volmer quenching phenomenon gave a ΚSV constant [1.92 (± 0.05) x 104 M-1] and kq constant [8.33 (± 0.2) x 1011 M-1s-1]. Molecular docking simulations on the crystal structure of BSA, calf thymus DNA, and DNA gyrase, as well as pharmacophore analysis for BSA target, were also employed to study in silico the ability of [VO(cur)(2,2´-bipy)(H2O)] to bind to these target bio-macromolecules and explain the observed in vitro activity. © 2021 Elsevier Inc.
Συγγραφείς:
Avgoulas, D.Ι.
Katsipis, G.
Halevas, E.
Geromichalou, E.G.
Geromichalos, G.D.
Pantazaki, A.A.
Περιοδικό:
Journal of Inorganic Biochemistry
Εκδότης:
ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
Λέξεις-κλειδιά:
albumin; bovine serum albumin; coordination compound; curcumin; DNA; DNA topoisomerase (ATP hydrolysing); oxovanadium(iv) curcumin complex; unclassified drug; calf thymus DNA; coordination compound; curcumin; DNA; DNA topoisomerase (ATP hydrolysing); Escherichia coli protein; ligand; protein binding; vanadium, antifungal activity; Article; association constant; base pairing; chemical structure; cheminformatics; comparative study; computer model; conformational transition; controlled study; crystal structure; cytotoxicity; DNA replication; DNA transcription; drug absorption; drug synthesis; elemental analysis; fluorescence; Fourier transform infrared spectroscopy; high performance liquid chromatography; hydrogen bond; hydrophobicity; in vitro study; macromolecule; molecular docking; Monte Carlo method; pharmacophore; protein binding; protein secondary structure; static electricity; ultraviolet visible spectroscopy; viscometry; X ray crystallography; animal; binding site; bovine; chemistry; drug effect; enzymology; Escherichia coli; hemolysis; human; metabolism; viscosity, Animals; Binding Sites; Cattle; Coordination Complexes; Curcumin; DNA; DNA Gyrase; Escherichia coli; Escherichia coli Proteins; Hemolysis; Humans; Ligands; Molecular Docking Simulation; Protein Binding; Serum Albumin, Bovine; Vanadium; Viscosity
DOI:
10.1016/j.jinorgbio.2021.111402
