In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models

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

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Official URL: https://doi.org/10.1016/j.heliyon.2023.e13685

Abstract

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.

Item Type: Article
Uncontrolled Keywords: Chalcones; Antiepileptic drugs; AEDs; Zebrafish
Subjects: Q Science > QD Chemistry
Divisions: Others > Non Sunway Academics
Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Sunway Biofunctional Molecules Discovery Centre [formerly Research Centre for Crystalline Materials until 2023]
Depositing User: Ms Yong Yee Chan
Related URLs:
Date Deposited: 15 Apr 2023 07:44
Last Modified: 15 Apr 2023 07:44
URI: http://eprints.sunway.edu.my/id/eprint/2176

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