Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog

Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the biolumine...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-07, Vol.23 (15), p.8271
Main Authors: González-Berdullas, Patricia, Pereira, Renato B., Teixeira, Cláudia, Silva, José Pedro, Magalhães, Carla M., Rodríguez-Borges, José E., Pereira, David M., Esteves da Silva, Joaquim C. G., Pinto da Silva, Luís
Format: Article
Language:English
Subjects:
Antitumor activity
Apoptosis
Bromination
Cancer therapies
Cell death
Chemotherapy
Crosstalk
Cytotoxicity
Decomposition
Gastric cancer
Investigations
Light
Lung cancer
Prostate
Toxicity
Tumors
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Summary:Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the bioluminescent system of marine Coelenterazine: Coelenterazine (Clz) itself, Coelenteramide (Clmd), and Coelenteramine (Clm). We have found that Clz derivatives possess variable anticancer activity toward gastric and lung cancer. Interestingly, we also found that both brominated Clmd (Br-Clmd) and Clm (Br-Clm) were the most potent anticancer compounds toward these cell lines, with this being the first report of the anticancer potential of these types of molecules. Interestingly, Br-Clm possessed some safety profile towards noncancer cells. Further evaluation revealed that the latter compound induced cell death via apoptosis, with evidence for crosstalk between intrinsic and extrinsic pathways. Finally, a thorough exploration of the chemical space of the studied Br-Clm helped identify the structural features responsible for its observed anticancer activity. In conclusion, a new type of compounds with anticancer activity toward gastric and lung cancer was reported and characterized, which showed interesting properties to be considered as a starting point for future optimizations towards obtaining suitable chemotherapeutic agents.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23158271