The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods
Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential ris...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/1/98 |
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| author | Karolina Lejwoda Anna Gumieniczek Agata Filip Beata Naumczuk |
| author_facet | Karolina Lejwoda Anna Gumieniczek Agata Filip Beata Naumczuk |
| author_sort | Karolina Lejwoda |
| collection | DOAJ |
| description | Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk of phototoxicity were examined using chemical, in silico and in vitro methods. The UV/VIS irradiated solutions of TIM at pH 1–13 were subjected to LC-UV and UPLC-HRMS/MS analyses showing pseudo first-order kinetics of degradation and several degradation products. The structures of these photodegradants were elucidated by fragmentation path analysis based on high resolution (HR) fragmentation mass spectra, and then used for toxicity evaluation using OSIRIS Property Explorer and Toxtree. Potential risk of phototoxicity was also studied using chemical tests for detecting ROS under UV/VIS irradiation and in vitro tests on BALB/c 3T3 mouse fibroblasts (MTT, NRU and Live/Dead tests). TIM was shown to be potentially phototoxic because of its UV/VIS absorptive properties and generation ROS during irradiation. As was observed in the MTT and NRU tests, the co-treatment of fibroblasts with TIM and UV/VIS light inhibited cell viability, especially when concentrations of the drug were higher than 50 µg/mL. |
| first_indexed | 2024-03-08T10:38:51Z |
| format | Article |
| id | doaj.art-d4898c2631e14d26be31f233e0838e61 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-08T10:38:51Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-d4898c2631e14d26be31f233e0838e612024-01-26T18:06:02ZengMDPI AGPharmaceuticals1424-82472024-01-011719810.3390/ph17010098The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro MethodsKarolina Lejwoda0Anna Gumieniczek1Agata Filip2Beata Naumczuk3Department of Medicinal Chemistry, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Medicinal Chemistry, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Cancer Genetics, Cytogenetics Laboratory, Medical University of Lublin, 20-080 Lublin, PolandInstitute of Organic Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, PolandTimolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk of phototoxicity were examined using chemical, in silico and in vitro methods. The UV/VIS irradiated solutions of TIM at pH 1–13 were subjected to LC-UV and UPLC-HRMS/MS analyses showing pseudo first-order kinetics of degradation and several degradation products. The structures of these photodegradants were elucidated by fragmentation path analysis based on high resolution (HR) fragmentation mass spectra, and then used for toxicity evaluation using OSIRIS Property Explorer and Toxtree. Potential risk of phototoxicity was also studied using chemical tests for detecting ROS under UV/VIS irradiation and in vitro tests on BALB/c 3T3 mouse fibroblasts (MTT, NRU and Live/Dead tests). TIM was shown to be potentially phototoxic because of its UV/VIS absorptive properties and generation ROS during irradiation. As was observed in the MTT and NRU tests, the co-treatment of fibroblasts with TIM and UV/VIS light inhibited cell viability, especially when concentrations of the drug were higher than 50 µg/mL.https://www.mdpi.com/1424-8247/17/1/98timololphotodegradationphototoxicityLC-UV and UPLC-HRMSROS generationin vitro tests |
| spellingShingle | Karolina Lejwoda Anna Gumieniczek Agata Filip Beata Naumczuk The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods Pharmaceuticals timolol photodegradation phototoxicity LC-UV and UPLC-HRMS ROS generation in vitro tests |
| title | The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods |
| title_full | The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods |
| title_fullStr | The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods |
| title_full_unstemmed | The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods |
| title_short | The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods |
| title_sort | study on timolol and its potential phototoxicity using chemical in silico and in vitro methods |
| topic | timolol photodegradation phototoxicity LC-UV and UPLC-HRMS ROS generation in vitro tests |
| url | https://www.mdpi.com/1424-8247/17/1/98 |
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