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

Autor: Mohd Fahmi MSA; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia., Swain P; Department of Biology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea., Ramli AH; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia., Wan Ibrahim WN; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.; Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia., Saleh Hodin NA; Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.; Centre of Foundation Studies for Agricultural Science, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia., Abu Bakar N; Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia., Tan YS; Research Centre for Crystalline Materials, School of Medical and Life Sciences, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia., Mohd Faudzi SM; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia., Kim CH; Department of Biology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea.
Jazyk: angličtina
Zdroj: Heliyon [Heliyon] 2023 Feb 11; Vol. 9 (2), pp. e13685. Date of Electronic Publication: 2023 Feb 11 (Print Publication: 2023).
DOI: 10.1016/j.heliyon.2023.e13685
Abstrakt: 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-(1 H -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 (GABA A , -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.
Competing Interests: The authors declare no conflict of interest.
(© 2023 The Authors.)
Databáze: MEDLINE
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