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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023
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Online Access:http://eprints.sunway.edu.my/2176/1/1-s2.0-s2405844023008927-main.pdf
http://eprints.sunway.edu.my/2176/
https://doi.org/10.1016/j.heliyon.2023.e13685
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spelling my.sunway.eprints.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
institution Sunway University
building Sunway Campus Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Sunway University
content_source Sunway Institutional Repository
url_provider http://eprints.sunway.edu.my/
language English
topic QD Chemistry
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
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.
format Article
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
title 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_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_sort in silico studies, x-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models
publisher Elsevier
publishDate 2023
url http://eprints.sunway.edu.my/2176/1/1-s2.0-s2405844023008927-main.pdf
http://eprints.sunway.edu.my/2176/
https://doi.org/10.1016/j.heliyon.2023.e13685
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