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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 a-amylase and a-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against a-glucosidase with IC 50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 mM, and a-amylase with IC 50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 mM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC 50 glucosidase ¼ 97.12 ± 0.35 mM and IC 50 amylase ¼ 2.97 ± 0.01 lM). 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 a-amylase and a-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.

Synthesis, biological evaluation, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives as new class of α-glucosidase and α-amylase inhibitors.

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