Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog
Patricia González-Berdullas1, Renato B Pereira2, Cláudia Teixeira2
1Centro de Investigação em Química (CIQUP), Instituto de Ciências Moleculares (IMS), Departamento de Geociências, Ambiente e Ordenamento do Território, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
Abstract:
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.
Insights
New halogenated Coelenterazine derivatives show potent anticancer activity against gastric and lung cancer. Brominated Coelenteramine (Br-Clm) demonstrated efficacy with a favorable safety profile, inducing apoptosis in cancer cells.
Area of Science:
- Marine natural products chemistry
- Medicinal chemistry
- Cancer biology
Background:
- Cancer treatment faces challenges due to side effects and limited therapeutic efficiency.
- The bioluminescent system of Coelenterazine offers a source for novel therapeutic molecules.
- Investigating halogenated derivatives of Coelenterazine components is a promising avenue for drug discovery.
Purpose of the Study:
- To explore the anticancer activity of halogenated derivatives of Coelenterazine (Clz), Coelenteramide (Clmd), and Coelenteramine (Clm).
- To identify potent anticancer compounds with potential therapeutic applications against specific cancer types.
- To characterize the mechanism of action and structure-activity relationships of promising candidates.
Main Methods:
- Synthesis and characterization of halogenated Coelenterazine derivatives.
- In vitro screening of compounds against gastric and lung cancer cell lines.
- Evaluation of cytotoxicity against non-cancer cells.
- Apoptosis induction assays and pathway analysis.
- Structure-activity relationship (SAR) studies.
Main Results:
- Coelenterazine derivatives exhibited variable anticancer activity against gastric and lung cancer cells.
- Brominated Coelenteramide (Br-Clmd) and brominated Coelenteramine (Br-Clm) showed the highest potency.
- Br-Clm demonstrated a favorable safety profile towards non-cancer cells.
- Br-Clm induced cancer cell death via apoptosis, involving both intrinsic and extrinsic pathways.
- Key structural features contributing to Br-Clm's anticancer activity were identified.
Conclusions:
- Halogenated Coelenterazine derivatives represent a novel class of anticancer agents.
- Br-Clm is a promising lead compound for the development of new chemotherapeutic agents against gastric and lung cancer.
- Further optimization of Br-Clm and related structures could lead to improved therapeutic efficacy and safety profiles.
More Related Videos
09:33Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
06:00Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
Related Concept Videos
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
01:27Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:29Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists
Phenothiazines, such as prochlorperazine...