Title: ChemiTumorTher –Marine Chemiluminescence as a Broad-Spectrum Anticancer Therapy with Enhanced Tumor-Selectivity and Activity
Funding/Source: €257 794 – Portuguese Foundation for Science (FCT)
Objective: We propose to develop and synthetize novel antitumor drugs based on the scaffold of Coelenterazine (CLZ), a marine chemiluminescent (CL) substrate. These drugs will be applied in a groundbreaking broad-spectrum cancer therapy with enhanced tumor-selectivity and activity. CL consists on the conversion of thermal energy into excitation energy with light-emission, due to a chemical reaction. The original feature of this project is the development of single-molecule CLZ mimetics that act as inactive prodrugs until intracellular self-activation by a cancer marker (overexpressed superoxide anion). This will trigger the CL reaction of this system, which instead of emitting light, will use its excitation energy toproduce the highly cytotoxic singlet oxygen. These mimetics are tumor-selective as they are only triggered by a cancer marker, while being broad-spectrum as singlet oxygen candestroy tumors by several pathways. In fact, preliminary data showed that the mimetics led to significant toxicity toward several cancer types (even for ones with poor prognosis, aslung and gastric cancer), while not affecting healthy cells.
Our role: WP Leaders
