The effects of the chemotherapeutic drug carboplatin on DNA: A chromatographic and theoretical investigation

Platinum-based anticancer drugs are the mainstay of the chemotherapy regimens designed to cure most cancers. One such complex currently in use, carboplatin, has shown significant antitumor activity. However, like all platinum-based antineoplastics, it also has considerable toxicities and can become less effective as cancer cell lines develop resistance to it. This research was conducted to better understand how carboplatin interacts with DNA to assist in oncology treatment protocols and to help innovate next-generation platinum-based antitumor drugs with less toxicity and less drug resistance. Modifications to the DNA dinucleotide phosphate 2'-deoxy-guanylyl-2'-deoxy-guanosine (dGpdG or GG) in the presence of carboplatin with varying drug-to-DNA ratios and concentrations were analyzed by reverse-phase High-Pressure Liquid Chromatography (RP-HPLC). Interactions of carboplatin near guanine were theoretically explored by density-functional theory (DFT) in Gaussian molecular modeling software. The findings of this study have highlighted the importance of the higher concentrations of carboplatin needed for the formation of drug-to-DNA adducts, which can disrupt cancer cell replication. This understanding could potentially guide the development of more effective cancer treatments in the future.