Platinum-acridine drugs, based on the foundations of cisplatin and carboplatin, are platinum (II) highly potent anticancer drugs, but they are also cytotoxic upon direct testing in animals. However, resistance occurs when certain proteins bypass these drugs with translesion synthesis, rendering the drugs ineffective. Platinum (IV) prodrugs are an improvement due to their octahedral structure which allows them to be more inert than the platinum (II) drugs who have a square planar VSEPR structure. An example of this is Satraplatin, whose two axial Diaceto ligands allow for a more successful attachment to targeting or functional groups within the cells as they’re only inert outside of the cells. Upon cell entrance, a reduction reaction transform the platinum (IV) back into platinum (II) active drug that then attaches to DNA. The significance of this work is to increase the efficacy of these anti-cancer agents by reducing the amount of side effects and the cytotoxicity to healthy cells.<br/>High-Performance Liquid Chromatography (HPLC), <sup>1</sup>H NMR, and X-Ray crystallography methods were used to monitor and determine the success of the reactions. Reactions were optimized using LCMS to determine conversion rates as well as purity.<br/>Further testing will be done to analyze the compound's reduction potential with the heavy metal antioxidant, GSH, found in cells. All three compounds will also be tested to assess their efficacy in lung cancer cell lines as well as in mice to determine their cytotoxicity and side effects in comparison to the precursor P8-A1.

Synthesis of platinum(IV)-acridine anticancer prodrugs

ACS Fall 2021

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