Targeting cancer through the inhibition of DNA unzipping Emmanuel Ohaekenyem 1 , Ikenna Onyido 2 1 Pure and Industrial Chemistry, Nnamdi Azikiwe University Awka, Nigeria, 2 Nnamdi Azikiwe University Awka, Nigeria By condensation process, a novel 1-10 phenanthroline-based macrocyclic ligand was produced. Fourier Transformed Infrared, Proton (1H), and Carbon 13 (13C) Nuclear Magnetic Resonance (NMR), High-Performance Liquid Chromatography (HPLC), and Thermal analyses were used to structurally analyze the produced compound. The compound's anticancer efficacy was assessed using Deoxyribonucleic Acid (DNA) and Guanine- Cytosine (GC) -rich Amplicon binding assays, as well as antioxidative assays. UV/Vis spectrophotometer, Polymerase Chain Reaction (PCR), and Gel Electrophoresis were used to assess their binding capacities. The compound demonstrated high DNA-Ligand binding activities, implying superior DNA intercalation and external binding capable of suppressing DNA PCR amplification. The interactions of the ligand with the GC-rich Amplicon resulted in binding constants of 6.00E+4/M and 1.00E+6/M with cell-free (cf)-DNA. The ligand demonstrated a lower binding constant with GC-rich Amplicon than with cf-DNA. The changes in Gibbs free energy for the ligand and its Ni-complex binding to cf-DNA were found to be -35.6 kJ/mol. Similarly, its interaction with GC-DNA amplicon resulted in changes in Gibbs free energy of -28.4 kJ/mol. At 500μg/ml, the compound had approximately 26% RSA and individual IC50s of 1.95mg/ml. Thermo Gravimetric Analysis (TGA) and differential thermal analysis revealed that it has good thermal stability (breakdown at an average of about 950K) and decomposes via first- order kinetics. The compound can aid in cell function regulation by altering transcription and/or interfering with cell replication and DNA repair processes.
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© The Author(s), 2023
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