Evaluation of the anticancer activity and chemiluminescence of a halogenated coelenterazine analog

Chemiluminescence is a remarkable process in which light is emitted due to a chemical reaction, without the need for photoexcitation. Among some of the most well-known chemiluminescent systems is that of marine Coelenterazine. Herein, we report the synthesis of a novel halogenated Coelenterazine analog, as well as the characterization of its potential anticancer activity and chemiluminescence. We have found that this analog is capable of significantly enhanced emission in aqueous solution when triggered by superoxide anion while being compatible with human cell lines. So, this compound presents great potential for the sensitive and dynamic sensing of a molecule of interest in biological media. Furthermore, the analysis of its cytotoxicity provided structural insight into the properties of brominated Coelenterazines, which were previously found to possess selective anticancer activity. Namely, the introduction of bromine heteroatoms is not enough to provide cyto-toxicity, while the introduction of electro-withdrawing groups eliminates all previously reported anticancer activity. Finally, while this compound is not active, its use in a combination approach allowed to improve the profile of a known chemotherapeutic agent. These results should be useful to guide future optimizations of halogenated Coelenterazine analogs.

Automated summary

Chemiluminescence is a fascinating process that allows light emission without the need for photoexcitation. In this study, a halogenated Coelenterazine analog was synthesized, and its potential anticancer activity and chemiluminescence were characterized. The results showed that this analog exhibited enhanced emission in aqueous solution when triggered by superoxide anions and was compatible with human cell lines. The analysis also provided insights into the cytotoxicity and structural properties of brominated Coelenterazines, which have selective anticancer activity. Furthermore, the combination approach with a known chemotherapeutic agent improved its profile. These findings are valuable for future optimizations of halogenated Coelenterazine analogs.