Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival
Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-infl...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/1420-3049/28/15/5696 |
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| author | Seung-Heon Shin Mi-Kyung Ye Mi-Hyun Chae Sang-Yen Geum Ahmed S. Aboraia Abu-Baker M. Abdel-Aal Wesam S. Qayed Hend A. A. Abd El-wahab Ola F. Abou-Ghadir Tarek Aboul-Fadl |
| author_facet | Seung-Heon Shin Mi-Kyung Ye Mi-Hyun Chae Sang-Yen Geum Ahmed S. Aboraia Abu-Baker M. Abdel-Aal Wesam S. Qayed Hend A. A. Abd El-wahab Ola F. Abou-Ghadir Tarek Aboul-Fadl |
| author_sort | Seung-Heon Shin |
| collection | DOAJ |
| description | Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96<sup>®</sup> aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases. |
| first_indexed | 2024-03-11T00:21:45Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:21:45Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9d319026c3ce4b48a6abe5567c0493ce2023-11-18T23:17:39ZengMDPI AGMolecules1420-30492023-07-012815569610.3390/molecules28155696Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and SurvivalSeung-Heon Shin0Mi-Kyung Ye1Mi-Hyun Chae2Sang-Yen Geum3Ahmed S. Aboraia4Abu-Baker M. Abdel-Aal5Wesam S. Qayed6Hend A. A. Abd El-wahab7Ola F. Abou-Ghadir8Tarek Aboul-Fadl9Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of KoreaDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of KoreaDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of KoreaDepartment of Otolaryngology-Head and Neck Surgery, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of KoreaDepartment of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptLidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96<sup>®</sup> aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.https://www.mdpi.com/1420-3049/28/15/5696lidocaine analoganti-inflammationpharmacophoreligand-based drug |
| spellingShingle | Seung-Heon Shin Mi-Kyung Ye Mi-Hyun Chae Sang-Yen Geum Ahmed S. Aboraia Abu-Baker M. Abdel-Aal Wesam S. Qayed Hend A. A. Abd El-wahab Ola F. Abou-Ghadir Tarek Aboul-Fadl Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival Molecules lidocaine analog anti-inflammation pharmacophore ligand-based drug |
| title | Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival |
| title_full | Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival |
| title_fullStr | Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival |
| title_full_unstemmed | Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival |
| title_short | Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival |
| title_sort | effects of lidocaine derived organic compounds on eosinophil activation and survival |
| topic | lidocaine analog anti-inflammation pharmacophore ligand-based drug |
| url | https://www.mdpi.com/1420-3049/28/15/5696 |
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