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

[Display omitted] •A halogenated Coelenterazine derivative is synthesized and characterized.•Enhanced emission in aqueous solution when triggered by superoxide anion.•Introduction of bromine heteroatoms is not enough to induce anticancer activity.•Replacing EDG with EWG groups at the phenyl moiety eliminates anticancer activity.•Use in combination improves the profile of a chemotherapeutic agent. 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 cytotoxicity, 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.