Novel Pyrrole-Based Thiazole Conjugates: Design, Synthesis, Antioxidant, Antidiabetic Assessment, Molecular Docking, Simulation, and In Silico ADME Studies
摘要
Objective: In the current study, novel heterocyclic molecules of pyrrole-conjugated thiazole were synthesized for the development of antidiabetic drugs. Methods: (E)-2-(2-((1-substituted-1H-pyrrol-2-yl)methylene)hydrazineyl)thiazole analogues (A1–A12) were synthesized by reacting thiosemicarbazide and substituted formyl pyrrole in ethanol to yield the intermediate 1-substituted pyrrol-2-carbaldehyde thiosemicarbazone, followed by the addition of α-bromoacetophenone in anhydrous ethanol and refluxing for 8 h. The synthesized derivatives were evaluated for antioxidant and antidiabetic activity. Results and Discussion: Compound A11 was found to be the most efficient antioxidant among all synthesized derivatives, with an IC50 value of 15.28 μg/mL. In the α-amylase inhibitory activity assay, derivatives A9 (IC50 = 2.10 ± 0.04 μg/mL), A7 (IC50 = 8.20 ± 0.04 μg/mL), and A11 (IC50 = 12.10 ± 0.04 μg/mL) demonstrated significantly higher potency, with activities surpassing that of acarbose (IC50 = 20.30 ± 0.20 μg/mL). Significant blood glucose lowering effects were displayed by compounds A9 and A11 (162 ± 0.21 and 176 ± 0.15 mg/dL, respectively). Conclusions: The appropriate molecular docking studies, ADME properties, and suitable binding interactions make the pyrrole-substituted thiazole analogues a promising structural motif for further clinical evaluation and the development of a new antidiabetic drug molecule.