In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models
Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023
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| Online Access: | http://eprints.sunway.edu.my/2176/ http://eprints.sunway.edu.my/2176/1/1-s2.0-s2405844023008927-main.pdf |
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| author | Muhammad Syafiq, Akmal Mohd Fahmi Swain, Puspanjali Amirah, Hani Ramli Wan Norhamidah, Wan Ibrahim Nur Atikah, Saleh Hodin Noraini, Abu Bakar Tan, Yee Seng * Siti Munirah, Mohd Faudzi Kim, Cheol-Hee |
| author_facet | Muhammad Syafiq, Akmal Mohd Fahmi Swain, Puspanjali Amirah, Hani Ramli Wan Norhamidah, Wan Ibrahim Nur Atikah, Saleh Hodin Noraini, Abu Bakar Tan, Yee Seng * Siti Munirah, Mohd Faudzi Kim, Cheol-Hee |
| author_sort | Muhammad Syafiq, Akmal Mohd Fahmi |
| building | SU Institutional Repository |
| collection | Online Access |
| description | Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (compound 8) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABAA, − 8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action. |
| first_indexed | 2025-11-14T21:19:50Z |
| format | Article |
| id | sunway-2176 |
| institution | Sunway University |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T21:19:50Z |
| publishDate | 2023 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | sunway-21762023-04-15T07:44:57Z http://eprints.sunway.edu.my/2176/ In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models Muhammad Syafiq, Akmal Mohd Fahmi Swain, Puspanjali Amirah, Hani Ramli Wan Norhamidah, Wan Ibrahim Nur Atikah, Saleh Hodin Noraini, Abu Bakar Tan, Yee Seng * Siti Munirah, Mohd Faudzi Kim, Cheol-Hee QD Chemistry Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (compound 8) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABAA, − 8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action. Elsevier 2023-02-02 Article PeerReviewed text en cc_by_nc_nd_4 http://eprints.sunway.edu.my/2176/1/1-s2.0-s2405844023008927-main.pdf Muhammad Syafiq, Akmal Mohd Fahmi and Swain, Puspanjali and Amirah, Hani Ramli and Wan Norhamidah, Wan Ibrahim and Nur Atikah, Saleh Hodin and Noraini, Abu Bakar and Tan, Yee Seng * and Siti Munirah, Mohd Faudzi and Kim, Cheol-Hee (2023) In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models. Heliyon, 9 (2). e13685. ISSN 2405-8440 https://doi.org/10.1016/j.heliyon.2023.e13685 10.1016/j.heliyon.2023.e13685 |
| spellingShingle | QD Chemistry Muhammad Syafiq, Akmal Mohd Fahmi Swain, Puspanjali Amirah, Hani Ramli Wan Norhamidah, Wan Ibrahim Nur Atikah, Saleh Hodin Noraini, Abu Bakar Tan, Yee Seng * Siti Munirah, Mohd Faudzi Kim, Cheol-Hee In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| title | In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| title_full | In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| title_fullStr | In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| title_full_unstemmed | In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| title_short | In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| title_sort | in silico studies, x-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models |
| topic | QD Chemistry |
| url | http://eprints.sunway.edu.my/2176/ http://eprints.sunway.edu.my/2176/ http://eprints.sunway.edu.my/2176/ http://eprints.sunway.edu.my/2176/1/1-s2.0-s2405844023008927-main.pdf |