Synthesis, Biophysical Interaction of DNA/BSA, Equilibrium and Stopped-Flow Kinetic Studies, and Biological Evaluation of bis(2-Picolyl)amine-Based Nickel(II) Complex

Abstract

Reaction of bis(2-picolyl)amine (BPA) with Ni(II) salt yielded [(BPA)NiCl2(H2O)] (NiBPA). The Ni(II) in NiBPA bound to a BPA ligand, two chloride, and one aqua ligands. Because most medications inhibit biological processes by binding to a specific protein, the stopped-flow technique was used to investigate DNA/protein binding in-vitro, and a mechanism was proposed. NiBPA binds to DNA/protein more strongly than BPA via a static quenching mechanism. Using the stopped-flow technique, a mechanism was proposed. BSA interacts with BPA via a fast reversible step followed by a slow irreversible step, whereas NiBPA interacts via two reversible steps. DNA, on the other hand, binds to BPA and NiBPA via the same mechanism through two reversible steps. Although BSA interacts with NiBPA much faster, NiBPA has a much higher affinity for DNA (2077 M) than BSA (30.3 M). Compared to NiBPA, BPA was found to form a more stable BSA complex. When BPA and NiBPA bind to DNA, the Ni(II) center was found to influence the rate but not the mechanism, whereas, for BSA, the Ni(II) center was found to change both the mechanism and the rate. Additionally, NiBPA exhibited significant cytotoxicity and antibacterial activity, which is consistent with the binding constants but not the kinetic stability. This shows that in our situation, biological activity is significantly more influenced by binding constants than by kinetic stability. Due to its selectivity and cytotoxic activity, complex NiBPA is anticipated to be used in medicine.

DNA Binding and Cleavage, Stopped-Flow Kinetic, Mechanistic, and Molecular Docking Studies of Cationic Ruthenium(II) Nitrosyl Complexes Containing “NS4” Core

“…The hydrogen bond acceptor sites of the DNA phosphate group in combination with DNA polymerase can thus be mimicked using the triazole template strand [ 53 ] or TSPH 2 , and this will have an effect on DNA bending, rigidity, and recognition. In a previous study [ 41 ], the docking results showed that BSA-[RuNOTSP] + with binding affinity (−7.27 kcal/mol) and BSA-TSPH 2 with binding affinity (−8.05 kcal/mol) are located in subdomain IA and it has recently been reported as a possible binding site for drugs on BSA [ 74 ].…”

“…As it is expected that the drug interaction will happen so quickly, a fast kinetic method is needed to find transient intermediates in the interaction pathway. We employed the stopped-flow technique in earlier studies [ 37 , 38 , 39 , 40 , 41 ], in which sample and reagent solutions were quickly mixed, and measurements were taken almost immediately after mixing. Using this technique, it was found that other factors, such as drug affinity and the kinetic stability of the DNA/protein–drug complex, are also essential for biological activity when examining how various drugs interacted with DNA and proteins.…”

Hydroxychloroquine-Loaded Chitosan Nanoparticles Induce Anticancer Activity in A549 Lung Cancer Cells: Design, BSA Binding, Molecular Docking, Mechanistic, and Biological Evaluation

“…We used a stopped-flow technique for carrying out a kinetic investigation of the binding process because it is thought that DNA/protein–drug interaction is a fast step. This method aids in identifying the kinetic characteristics of the phases leading to intermediate species and ultimately obtaining an interaction mechanism [ 41 , 42 , 43 , 44 , 45 , 46 ], The geometrically optimized parameters (bond lengths, bond angles, and dihedral angles) were computed using DFT/B3LYP theory on the chitosan moiety and HCQ. Docking simulation will be used in order to confirm the spectroscopic results of the binding of HCQ to the BSA structure and the formation of the HCQ–BSA complex.…”