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Acridine derivatives such as m-amsacrine (m-AMSA) are known to intercalate deoxyribonucleic acid (DNA). Their action targets the growth, function, and replication of cancer cells. Because of this, they are primarily used as anticancer and antimalaria drugs. Unfortunately, due to the low half-life m-AMSA possesses because of the ease of hydrolysis of the carbon 9-nitrogen bond (C9-N bond), large concentrations of the drug are needed to be pharmaceutically effective. This results in a large concentration of toxic aniline byproducts. To reduce the rate of hydrolysis but still maintain the binding to DNA, a modification to the m-AMSA structure was made. A series of m-AMSA derivatives with a hydroxylamine linkage between the acridine nucleus and the C9-pendant was prepared via a linear three-step synthesis. Commercially available aryl bromides were coupled with hydroxylamine using catalytic palladium. Once the resulting O-substituted hydroxylamine was hydrolyzed, the product could be coupled with 9-chloroacridine to form the target compounds. Spectroscopic methods such as Proton nuclear magnetic resonance spectroscopy (1H NMR), Carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR), 1H Correlation Spectroscopy (COSY), and heteronuclear single-quantum coherence (HSQC) were used to determine the purity and structure of each target derivative. The target derivatives will be analyzed and evaluated for their ability to bind DNA through thermal denaturation. A trial with DNA in a phosphate buffer through thermal denaturation was conducted to make a baseline for the thermal denaturation. The baseline showed that the melting point of calf-thymus DNA in the specific phosphate buffer system ranged between 68-71°C.