Presenting Author Moravian University Easton, Pennsylvania
Transition metal–based chemotherapeutics have been used to treat a variety of cancers since the 1960s with cisplatin being the most prominent of these drugs used in a clinical setting. Many cancers become chemoresistant to cisplatin, so there is currently a need to synthesize and explore the anticancer abilities of other transition metal complexes. Rhodium, one of the six platinum–group metals, demonstrates cytotoxic effects in cancer cells in the form of dirhodium tetraacetate (Rh2A4). However, Rh2A4 is known to be less cytotoxic than cisplatin in HeLa cervical cancer cells. This research aims to modify Rh2A4 to increase its cytotoxicity to that of cisplatin. One of the acetate ligands of Rh2A4 was selectively replaced with 6-maleimidohexanoic acid (M) to form a dirhodium triacetate maleimide (Rh2A3M) complex. Maleimides are known to readily react with alkylamines (R-NH2) under basic conditions to produce amine conjugates. Alkylamines were chosen because of this reactivity and because their presence in a variety of metabolic and physiological processes may aid in the uptake of the dirhodum complex in cancer cells. The Rh2A3M complex was successfully reacted with four alkylamines: benzylamine, cyclohexylamine, ethanolamine, and glucosamine. This reaction was done in a 1:10 molar ratio in a phosphate buffer of pH 7.25 at room temperature for 72 hours to form subsequent Rh2A3M-NH-R complexes. The crude reaction mixture was then purified by preparative HPLC and characterized via 1H 1D NMR. A new screening method was developed using MTT reagent to compare the cellular viability of HeLa cervical cancer cells treated with the four crude reaction mixtures and the four HPLC purified Rh2A3M-NH-R complexes. Each pure complex had a similar percent cellular viability to its corresponding crude reaction mixture. This procedure will allow for future screens of many Rh2A3M + R-NH2 crude reaction mixtures to indicate cytotoxicity of Rh2A3M-NH-R products without the need for the purification and characterization steps. Out of the four pure complexes, Rh2A3M-cyclohexylamine was found to be the most cytotoxic at ~20 μM, suggesting it is comparable in cytotoxicity to cisplatin. Current work is focused on the determination of the IC50 value for this complex to definitively compare its cytotoxicity to cisplatin.
Support or Funding Information
This work was supported by Moravian University’s Department of Chemistry; Department of Biological Sciences; and Student Opportunities for Academic Research (SOAR) program.
This work was supported by Moravian Universityamp;rsquo;s Department of Chemistry; Department of Biological Sciences; and Student Opportunities for Academic Research (SOAR) program.
