title: Spectroscopic, biological, and molecular modeling studies on the interactions of [Fe(III)-meloxicam] with G-quadruplex DNA and investigation of its release from bovine serum albumin (BSA) nanoparticles.
abstract: The guanine-rich sequence, specifically in DNA, telomeric DNA, is a potential target of anticancer drugs. In this work, a mononuclear Fe(III) complex containing two meloxicam ligands was synthesized as a G-quadruplex stabilizer. The interaction between the Fe(III) complex and G-quadruplex with sequence of 5'-G3(T2AG3)3-3' (HTG21) was investigated using spectroscopic methods, molecular modeling, and polymerase chain reaction (PCR) assays. The spectroscopic methods of UV-vis, fluorescence, and circular dichroism showed that the metal complex can effectively induce and stabilize G-quadruplex structure in the G-rich 21-mer sequence. Also, the binding constant between the Fe(III) complex and G-quadruplex was measured by these methods and it was found to be 4.53(±0.30) × 10(5) M(-1)). The PCR stop assay indicated that the Fe(III) complex inhibits DNA amplification. The cell viability assay showed that the complex has significant antitumor activities against Hela cells. According to the UV-vis results, the interaction of the Fe(III) complex with duplex DNA is an order of magnitude lower than G-quadruplex. Furthermore, the release of the complex incorporated in bovine serum albumin nanoparticles was also investigated in physiological conditions. The release of the complex followed a bi-phasic release pattern with high and low releasing rates at the first and second phases, respectively. Also, in order to obtain the binding mode of the Fe(III) complex with G-quadruplex, molecular modeling was performed. The molecular docking results showed that the Fe(III) complex was docked to the end-stacked of the G-quadruplex with a π-π interaction, created between the meloxicam ligand and the guanine bases of the G-quadruplex.
authors.affiliation: a Department of Chemistry , Isfahan University of Technology , Isfahan 84156-83111 , Iran.
authors.forename: Malihe
authors.initials: M
authors.lastname: Ebrahimi
authors.affiliation: a Department of Chemistry , Isfahan University of Technology , Isfahan 84156-83111 , Iran.
authors.forename: Taghi
authors.initials: T
authors.lastname: Khayamian
authors.affiliation: a Department of Chemistry , Isfahan University of Technology , Isfahan 84156-83111 , Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Hadadzadeh
authors.affiliation: b Department of Agricultural Biotechnology, College of Agriculture , Isfahan University of Technology , Isfahan 84156-83111 , Iran.
authors.forename: Badraldin Ebrahim
authors.initials: BE
authors.lastname: Sayed Tabatabaei
authors.affiliation: a Department of Chemistry , Isfahan University of Technology , Isfahan 84156-83111 , Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Jannesari
authors.affiliation: b Department of Agricultural Biotechnology, College of Agriculture , Isfahan University of Technology , Isfahan 84156-83111 , Iran.
authors.forename: Ghazale
authors.initials: G
authors.lastname: Khaksar
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry*; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D000077239:Meloxicam; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D013843:Thiazines / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D005290:Ferric Compounds; D013843:Thiazines; D013844:Thiazoles; D012710:Serum Albumin, Bovine; D004247:DNA; D000077239:Meloxicam
keywords: BSA nanoparticles; G-quadruplex DNA; PCR; cell culture; docking; molecular dynamics simulation