Investigation of the Anticancer and Drug Combination Potential of Brominated Coelenteramines toward Breast and Prostate Cancer

Cancer is a very challenging disease to treat, both in terms of therapeutic efficiency and harmful side effects, which continues to motivate the pursuit for novel molecules with potential anticancer activity. Herein, we have designed, synthesized, and evaluated the cytotoxicity of different brominated coelenteramines, which are metabolic products and synthesis precursors of the chemi-/bioluminescent system of marine coelenterazine. The evaluation of the anticancer potential of these molecules was carried out for both prostate and breast cancer, while also exploring their potential for use in combination therapy. Our results provided further insight into the structure-activity relationship of this type of molecule, such as their high structural specificity, as well highlighting the 4-bromophenyl moiety as essential for the anticancer activity. The obtained data also indicated that, despite their similarity, the anticancer activity displayed by both brominated coelenteramines and coelenterazines should arise from independent mechanisms of action. Finally, one of the studied coelenteramines was able to improve the profile of a known chemotherapeutic agent, even at concentrations in which its anticancer activity was not relevant. Thus, our work showed the potential of different components of marine chemi-/bioluminescent systems as novel anticancer molecules, while providing useful information for future optimizations.

Automated summary

Cancer is a challenging disease to treat, and this study focuses on the design, synthesis, and evaluation of different brominated coelenteramines as potential anticancer molecules. The results highlight the importance of the 4-bromophenyl moiety for their anticancer activity and suggest independent mechanisms of action compared to coelenterazines. One of the studied coelenteramines showed promise in improving the profile of a known chemotherapeutic agent.