Towards Safer Epirubicin Based Anti-Cancer Treatments

Towards Safer Epirubicin Based Anti-Cancer Treatments

Alvin Sherman Library

Epirubicin is a widely used anticancer agent whose mechanism of action (DNA intercalation leading to disruption of the double-stranded helical structure) has been extensively studied. Despite its clinical effectiveness, epirubicin is associated with significant side effects that limit its therapeutic window. In this work, we investigated the interaction of epirubicin with a circular double-stranded plasmid DNA (2686 bp) in the presence and absence of 5-amino-4-imidazolecarboxamide (AIC). Spectroscopic studies combined with a modified Stern-Volmer methodology were used to determine binding constants. The results indicate that stepwise addition of AIC enhances epirubicin intercalation, yielding a higher DNA-epirubicin binding constant compared to epirubicin alone. Free energy calculations further support an increased stabilization energy in the ternary DNA-epirubicin-AIC system. These findings suggest a potential strategy to improve the efficacy of epirubicin while mitigating its toxicity, offering insight into the design of novel anticancer treatments with reduced side effects.