The Affinity of Carboplatin to B-Vitamins and Nucleobases

Abstract

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

G-Protein-Coupled Receptors Mediate Modulations of Cell Viability and Drug Sensitivity by Aberrantly Expressed Recoverin 3 within A549 Cells

“…The cytotoxicity induced by DTX in the 2D-cultured A549 Rec was increased as compared with control MOCK cells as observed in our previous studies [22,23]. However, in contrast, significant differences in the anti-tumor drug sensitivities by CRDCA or PEM were not observed between A549 MOCK and A549 Rec, suggesting that aberrantly expressed Rec may influence specific but not all mechanisms by anti-tumor drug, i.e., the inhibition of cellular mitosis mechanisms by DTX [24] rather than modulations of DNA-related metabolisms by CRDCA [25] and PEM [26].…”

Isolated Pyridoxine Deficiency Presenting as Peripheral Neuropathy Post-chemotherapy

“…Carboplatin is a platinum-based chemotherapeutic drug used for the treatment of solid tumors, which bind to DNA nucleobases, leading to replication and transcription suppression, apoptosis, or necrosis in tumor cells [ 7 ]. The commonly seen adverse effects include myelosuppression, renal insufficiency, and peripheral neuropathy seen in 4%-6% of patients posttreatment [ 8 , 9 ]. Spectroscopic studies have revealed complex formation between pyridoxine and carboplatin due to structural similarity to adenine and guanine, leading to a decrease in the maximum absorbance of pyridoxine relative to its baseline [ 7 ].…”

Metallodrugs: Mechanisms of Action, Molecular Targets and Biological Activity

“…The work by Szefler et al presents a computational study on the affinity of carboplatin to B vitamins, aiming to establish if the vitamins—as components of beet and carrot juice—could possibly lead to a reduction in the efficacy of this drug. Their data indicated that carboplatin can bind vitamins B3 and B6, and their computational prediction was also verified by experimental data [ 16 ].…”