Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish
Safety is one of the most important and critical issues in drug development. Many drugs were abandoned in clinical trials and retracted from the market because of unknown side effects. Cardiotoxicity is one of the most common reasons for drug retraction due to its potential side effects, i.e., induc...
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MDPI AG
2019-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/6/566 |
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| author | Bonifasius Putera Sampurna Fiorency Santoso Jia-Hau Lee Wen-Hao Yu Chin-Chung Wu Gilbert Audira Stevhen Juniardi Jung-Ren Chen Ying-Ting Lin Chung-Der Hsiao |
| author_facet | Bonifasius Putera Sampurna Fiorency Santoso Jia-Hau Lee Wen-Hao Yu Chin-Chung Wu Gilbert Audira Stevhen Juniardi Jung-Ren Chen Ying-Ting Lin Chung-Der Hsiao |
| author_sort | Bonifasius Putera Sampurna |
| collection | DOAJ |
| description | Safety is one of the most important and critical issues in drug development. Many drugs were abandoned in clinical trials and retracted from the market because of unknown side effects. Cardiotoxicity is one of the most common reasons for drug retraction due to its potential side effects, i.e., inducing either tachycardia, bradycardia or arrhythmia. The zebrafish model could be used to screen drug libraries with potential cardiotoxicity in a high-throughput manner. In addition, the fundamental principles of replacement, reduction, and refinement of laboratory animal usage, 3R, could be achieved by using zebrafish as an alternative to animal models. In this study, we used a simple ImageJ-based method to evaluate and screen 70 ion channel ligands and successfully identify six compounds with strong cardiotoxicity in vivo. Next, we conducted an in silico-based molecular docking simulation to elucidate five identified compounds that might interact with domain III or domain IV of the <i>Danio rerio</i> L-type calcium channel (LTCC), a known pharmaceutically important target for arrhythmia. In conclusion, in this study, we provide a web lab and dry lab combinatorial approach to perform in vivo cardiotoxicity drug screening and in silico mechanistic studies. |
| first_indexed | 2024-03-12T20:08:50Z |
| format | Article |
| id | doaj.art-a636ec15011a42e6a18420956bdc21ee |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T20:08:50Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a636ec15011a42e6a18420956bdc21ee2023-08-02T01:53:00ZengMDPI AGCells2073-44092019-06-018656610.3390/cells8060566cells8060566Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in ZebrafishBonifasius Putera Sampurna0Fiorency Santoso1Jia-Hau Lee2Wen-Hao Yu3Chin-Chung Wu4Gilbert Audira5Stevhen Juniardi6Jung-Ren Chen7Ying-Ting Lin8Chung-Der Hsiao9Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, TaiwanDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, TaiwanDepartment of Biological Science & Technology College of Medicine, I-Shou University, Kaohsiung 82445, TaiwanDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, TaiwanSafety is one of the most important and critical issues in drug development. Many drugs were abandoned in clinical trials and retracted from the market because of unknown side effects. Cardiotoxicity is one of the most common reasons for drug retraction due to its potential side effects, i.e., inducing either tachycardia, bradycardia or arrhythmia. The zebrafish model could be used to screen drug libraries with potential cardiotoxicity in a high-throughput manner. In addition, the fundamental principles of replacement, reduction, and refinement of laboratory animal usage, 3R, could be achieved by using zebrafish as an alternative to animal models. In this study, we used a simple ImageJ-based method to evaluate and screen 70 ion channel ligands and successfully identify six compounds with strong cardiotoxicity in vivo. Next, we conducted an in silico-based molecular docking simulation to elucidate five identified compounds that might interact with domain III or domain IV of the <i>Danio rerio</i> L-type calcium channel (LTCC), a known pharmaceutically important target for arrhythmia. In conclusion, in this study, we provide a web lab and dry lab combinatorial approach to perform in vivo cardiotoxicity drug screening and in silico mechanistic studies.https://www.mdpi.com/2073-4409/8/6/566zebrafishheartion channel ligandcardiotoxicitymolecular docking |
| spellingShingle | Bonifasius Putera Sampurna Fiorency Santoso Jia-Hau Lee Wen-Hao Yu Chin-Chung Wu Gilbert Audira Stevhen Juniardi Jung-Ren Chen Ying-Ting Lin Chung-Der Hsiao Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish Cells zebrafish heart ion channel ligand cardiotoxicity molecular docking |
| title | Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish |
| title_full | Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish |
| title_fullStr | Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish |
| title_full_unstemmed | Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish |
| title_short | Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish |
| title_sort | cardiac rhythm and molecular docking studies of ion channel ligands with cardiotoxicity in zebrafish |
| topic | zebrafish heart ion channel ligand cardiotoxicity molecular docking |
| url | https://www.mdpi.com/2073-4409/8/6/566 |
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