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 fluor...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Published: |
Elsevier
2023
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| Online Access: | http://psasir.upm.edu.my/id/eprint/109225/ |
| _version_ | 1848865315229794304 |
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| author | Mohd Fahmi, Muhammad Syafiq Akmal Swain, Puspanjali Ramli, Amirah Hani Wan Ibrahim, Wan Norhamidah Saleh Hodin, Nur Atikah Abu Bakar, Noraini Tan, Yee Seng Mohd Faudzi, Siti Munirah Kim, Cheol-Hee |
| author_facet | Mohd Fahmi, Muhammad Syafiq Akmal Swain, Puspanjali Ramli, Amirah Hani Wan Ibrahim, Wan Norhamidah Saleh Hodin, Nur Atikah Abu Bakar, Noraini Tan, Yee Seng Mohd Faudzi, Siti Munirah Kim, Cheol-Hee |
| author_sort | Mohd Fahmi, Muhammad Syafiq Akmal |
| building | UPM 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 | 2025-11-15T14:02:45Z |
| format | Article |
| id | upm-109225 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T14:02:45Z |
| publishDate | 2023 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1092252024-08-27T04:19:27Z http://psasir.upm.edu.my/id/eprint/109225/ In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models Mohd Fahmi, Muhammad Syafiq Akmal Swain, Puspanjali Ramli, Amirah Hani Wan Ibrahim, Wan Norhamidah Saleh Hodin, Nur Atikah Abu Bakar, Noraini Tan, Yee Seng Mohd Faudzi, Siti Munirah Kim, Cheol-Hee 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 Article PeerReviewed Mohd Fahmi, Muhammad Syafiq Akmal and Swain, Puspanjali and Ramli, Amirah Hani and Wan Ibrahim, Wan Norhamidah and Saleh Hodin, Nur Atikah and Abu Bakar, Noraini and Tan, Yee Seng and Mohd Faudzi, Siti Munirah 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). art. no. e13685. pp. 1-18. ISSN 2405-8440 https://linkinghub.elsevier.com/retrieve/pii/S2405844023008927 10.1016/j.heliyon.2023.e13685 |
| spellingShingle | Mohd Fahmi, Muhammad Syafiq Akmal Swain, Puspanjali Ramli, Amirah Hani Wan Ibrahim, Wan Norhamidah Saleh Hodin, Nur Atikah Abu Bakar, Noraini Tan, Yee Seng Mohd Faudzi, Siti Munirah 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 |
| url | http://psasir.upm.edu.my/id/eprint/109225/ http://psasir.upm.edu.my/id/eprint/109225/ http://psasir.upm.edu.my/id/eprint/109225/ |