Transition metal complexes of 6‐mercaptopurine: Characterization, Theoretical calculation, DNA‐Binding, molecular docking, and anticancer activity

Abstract

6‐mercaptopurine (6‐MP) is used for treating various cancers and autoimmune disorders. A few examples of transition metal complexes of 6‐MP have been shown to enhance its anticancer activity, but many remain untested. We isolated five highly stable and colored metal complexes of 6‐MP and confirmed their structures by elemental analysis, spectral, and thermal techniques. Infrared (IR) spectra revealed that 6‐MP is a bidentate ligand that interacts through sulfur and pyrimidine nitrogen in a 1:2 (M:L) molar ratio. The magnetic susceptibility and electron paramagnetic resonance (EPR) spectra for the Cu(II) complex revealed an octahedral arrangement around the metal ion with strong covalent bonding. The fully optimized geometries of the metal structures obtained using density function theory (DFT)/B3LYP calculations were used to verify the structural and biological features. DNA titration revealed that the octahedral Cu(II) complex has a critical binding constant value of Kb = 8 × 105. Docking studies using three different cancer protein receptors were used to predict the biological applications of the synthesized drug‐metal complexes. Finally, cytotoxicity assays against a myeloma cancer cell line (MM) and a colon cancer cell line (Caco‐2) revealed favorable anticancer activity for the copper complex, exceeding that of the gold‐standard chemotherapeutic cisplatin.

Synthesis and theoretical calculations of metal-antibiotic chelation with thiamphenicol:in vitroDNA and HSA binding, molecular docking, and cytotoxicity studies

“…HOMO and LUMO energies were obtained and used to calculate essential quantum parameters using the following equations: energy gap (E gap = E LUMO À E HOMO ), absolute electronegativities (w = ÀE HOMO + E LUMO /2), absolute hardness (Z = E LUMO À E HOMO /2), chemical potentials (m = Àw), global softness (S = 1/2Z), and global electrophilicity (o = p 2 /2Z). 12,13 MEP maps were projected by applying the B3LYP/LANL2DZ level within DFT.…”

“…We used the docking process described in previous work. 12 After finding potential binding sites on the protein using Site Finder, the bound water, ligands and cofactors were removed from the protein. Then, the metal complexes were minimized to the lowest energy using the MMFF94 force field.…”

“…2 Some transition metals are essential components of biological systems, playing diverse roles including as cofactors in the enzyme oxidation process, controlling the geometry of the enzymic active sites, and activating enzymatic reactions. 3 Moreover, they are present in vitamins such as Co(II) in B 12 . Copper is essential for nervous system development and it exists in many enzymes and proteins with a range of functions such as in energy metabolism. 4 Zinc is the most abundant transition metal in the human body playing several important roles including in immunity and metabolism, and is crucial for the function of more than 300 enzymes.…”

Lossen Rearrangement of p-Toluenesulfonates of N-Oxyimides in Basic Condition, Theoretical Study, and Molecular Docking

“…Our hypothesis is the results of the rearrangement could bind to active site of HLE and have the ability to inhibit of serine proteinases. Molecular docking is common and practical method to study the mechanistic pathway by placing the investigated molecule in the possible binding site of the target specific region (Sharfalddin et al, 2020). Therefore, we test the binding ability of the sulfonic molecules and the product complexes toward the Human Leukocyte Elastase (HLE) by the molecular docking approach.…”

“…Molecular operation environment software (MOE) has utilized to dock the complexes toward Human Leukocyte Elastase (PDB = 1EAT). We used the docking protocol that has been descried in our previous work (Sharfalddin et al, 2020). After the crystal structure has downloaded from the PDB www.rcsb.org, the water molecules, co-ligand and the metal ions have been removed.…”