Biological, toxicological and molecular docking evaluations of isoxazoline-thiazolidine-2,4-dione analogues as new class of anti-hyperglycemic agents.

Autor:	Fettach S; Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco., Thari FZ; Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculty of Science, B.P. 1014, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University in Rabat, Rabat, Morocco., Hafidi Z; Department of Surfactants and Nanobiotechnology, IQAC-CSIC, c/Jordi Girona, Barcelona, Spain., Karrouchi K; Laboratory of Analytical Chemistry and Bromatology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco., Bouathmany K; Biology and Molecular Research Unit, Department of Life Sciences, National Center for Energy, Nuclear Science and Technology (CNESTEN), Rabat, Morocco., Cherrah Y; Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco., El Achouri M; Laboratoire de Physico-Chimie des Matériaux Inorganiques et Organiques, Centre des Sciences des Matériaux, Ecole Normale Supérieure-Rabat, Mohammed V University, Rabat, Morocco., Benbacer L; Biology and Molecular Research Unit, Department of Life Sciences, National Center for Energy, Nuclear Science and Technology (CNESTEN), Rabat, Morocco., El Mzibri M; Biology and Molecular Research Unit, Department of Life Sciences, National Center for Energy, Nuclear Science and Technology (CNESTEN), Rabat, Morocco., Sefrioui H; Moroccan Foundation for Science, Innovation & Research (MAScIR), Centre de Biotechnologie Médicale, Rabat, Morocco., Bougrin K; Equipe de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculty of Science, B.P. 1014, Geophysics, Natural Patrimony and Green Chemistry (GEOPAC) Research Center, Mohammed V University in Rabat, Rabat, Morocco.; Chemical and Biochemical Sciences Green Process Engineering (CBS), Mohammed VI Polytechnic University (UM6P), Benguerir, Morocco., Faouzi MEA; Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.
Jazyk:	angličtina
Zdroj:	Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 Feb; Vol. 41 (3), pp. 1072-1084. Date of Electronic Publication: 2021 Dec 26.
DOI:	10.1080/07391102.2021.2017348
Abstrakt:	In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1 H-NMR, 13 C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC 50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC 50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC 50 glucosidase = 97.12 ± 0.35 µM and IC 50 amylase = 2.97 ± 0.01 μM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.
Databáze:	MEDLINE
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