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

Reaction of bis(2-picolyl)amine (BPA) with Ni(II) salt yielded [(BPA)NiCl(2)(H(2)O)] (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...

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Detalles Bibliográficos
Autores principales: Ramzy, Esraa, Ibrahim, Mohamed M., El-Mehasseb, Ibrahim M., Ramadan, Abd El-Motaleb M., Elshami, Fawzia I., Shaban, Shaban Y., van Eldik, Rudi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680484/
https://www.ncbi.nlm.nih.gov/pubmed/36412701
http://dx.doi.org/10.3390/biomimetics7040172
Descripción
Sumario:Reaction of bis(2-picolyl)amine (BPA) with Ni(II) salt yielded [(BPA)NiCl(2)(H(2)O)] (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.