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.

G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs

“…The octahedral Fe(III) complex 159 contains two meloxicam ligands and also induces and stabilizes the hTel G4 structure with good affinity and selectivity as shown by UV/Vis, fluorescence and CD spectroscopy as well as PCR-stop assays. 106 Although the binding constant between 159 and hTel G4 (4.53 × 10 5 M −1 ) is smaller than that of most Pt(II) complexes, it is an order of magnitude higher than that for the interaction with duplex DNA. According to molecular modelling, the binding mode between the Fe(III) complex and the G4 structure is end-stacking of the meloxicam ligand on the terminal G-quartet.…”

“…13 Octahedral ruthenium(II) polypyridyl complexes and a Fe(III) complex containing two meloxicam ligands reported as G4-ligands. [94][95][96][97][98][99][100][101][102][103][104]106 Because of the octahedral geometry of these metal complexes, the metal centre and the entire molecule is unlikely to end-stack on or intercalate into the G-quartets. It is actually the aromatic ligand with its large π-delocalized planar surface, such as the meloxicam and the dppz ligand, that adopts the end-stacking or intercalation binding mode with G-quartets.…”

Spectroscopic and molecular docking studies on the binding mechanism of Mobic and lipase

“…in addition to the treatment of in-flammatory diseases, Mobic also has a good effect on relieving physical pain in patients. [4]…”

Spectroscopic study on the mechanism of meloxicam and α-amylase

“…This drug is widely used in daily life and it is a very common drug for the treatment of rheumatoid arthritis. in addition to the treatment of inflammatory diseases, MEL also has a good effect on relieving physical pain in patients [4] . Figure 1.…”