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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Veröffentlicht in: | International journal of molecular sciences 2022-07, Vol.23 (15), p.8271 |
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creator | 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 |
description | 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. |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23158271</identifier><identifier>PMID: 35955406</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Antitumor activity ; Apoptosis ; Bromination ; Cancer therapies ; Cell death ; Chemotherapy ; Crosstalk ; Cytotoxicity ; Decomposition ; Gastric cancer ; Investigations ; Light ; Lung cancer ; Prostate ; Toxicity ; Tumors</subject><ispartof>International journal of molecular sciences, 2022-07, Vol.23 (15), p.8271</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. 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G.</creatorcontrib><creatorcontrib>Pinto da Silva, Luís</creatorcontrib><title>Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog</title><title>International journal of molecular sciences</title><description>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. 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G.</au><au>Pinto da Silva, Luís</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog</atitle><jtitle>International journal of molecular sciences</jtitle><date>2022-07-27</date><risdate>2022</risdate><volume>23</volume><issue>15</issue><spage>8271</spage><pages>8271-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><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. 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subjects | Antitumor activity Apoptosis Bromination Cancer therapies Cell death Chemotherapy Crosstalk Cytotoxicity Decomposition Gastric cancer Investigations Light Lung cancer Prostate Toxicity Tumors |
title | Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog |
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