Work

Design, synthesis, and biological evaluation of novel pyrazole-phenylcarbamothioyl derivatives as multitarget antidiabetic agents: in vitro and in silico studies

Year: 2026

Type: article

Abstract: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that requires therapeutic strategies targeting multiple enzymes involved in carbohydrate-digestion and glucose metabolism, such as α-amylase, α-glucosidase , and aldose reductase . In the present study, a series of twelve new ethyl 5-hydroxy-1-phenyl-4-(phenylcarbamothioyl)-1 H -pyrazole-3-carboxylate derivatives 5(a-l) were synthesized and structurally characterized by 1 H NMR, 13 C NMR, FT-IR, and Mass spectrometry. Single-crystal X-ray diffraction analysis of compound 5e confirmed a monoclinic system with P2 1 /n space group. Further, all the compounds were evaluated for inhibitory activity against α-amylase , α-glucosidase , and aldose reductase . Among the tested compounds, 5j exhibited the α-glucosidase inhibitory activity with an IC 50 of 143.20 ± 0.80 μ M compared with acarbose (IC 50 = 200.12 ± 2.25 μM), while compound 5k exhibited α-amylase inhibition with an IC 50 of 82.54 ± 0.85 μ M , compared with acarbose (120.23 ± 1.2 μM). Compound 5j demonstrated the strongest aldose reductase inhibition ( IC 50 = 15.32 ± 0.94 μ M ), which was comparable to that of quercetin ( IC 50 = 16.14 ± 0.93 μ M ). Molecular docking supported the experimental observations by exhibiting favourable interactions of the active compounds within the active site of targeted enzymes. Structure-activity relationship analysis indicated that the contribution of pyrazole, thioamide, and hydroxyl functionalities to enzyme inhibition. Furthermore, the predicted in silico ADMET studies suggested favourable drug-likeliness and pharmacokinetic properties. Collectively, compounds 5j and 5k represent lead compounds identified for the investigated enzyme targets and warrant further structural optimization and biological evaluation.

Source: Results in Chemistry

DOI: 10.1016/j.rechem.2026.103998