Design, synthesis, and biological evaluation of novel pyrazole-phenylcarbamothioyl derivatives as multitarget antidiabetic agents:
5 affiliations
- 1Department of Studies in Chemistry, Manasagangotri, University of Mysore, Karnataka, 570 006, India
- 2Department of Chemistry, Poornaprajna College, Shree Adamaru Matha Education Council, Mangalore University, Karnataka, India
- 3Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570 015, India
- 4Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru, Karnataka, 570 015, India; Co-corresponding author.
- 5Department of Studies in Chemistry, Manasagangotri, University of Mysore, Karnataka, 570 006, India; Corresponding author.
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 μM 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 μM , compared with acarbose (120.23 ± 1.2 μM). Compound 5j demonstrated the strongest aldose reductase inhibition ( IC 50 = 15.32 ± 0.94 μM ), 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 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.
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BibTeX
@article{madalambika2026design,
title = {{Design, synthesis, and biological evaluation of novel pyrazole-phenylcarbamothioyl derivatives as multitarget antidiabetic agents:}},
author = {Madalambika and A.C. Kumar and P.M. BharathKumar and J. Rangaswamy and N. Akshaya Simha and Ramith Ramu and Nagaraja Naik},
journal = {Results in Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.rechem.2026.103998},
url = {https://doi.org/10.1016/j.rechem.2026.103998},
note = {CC BY},
}
RIS
TY - JOUR
TI - Design, synthesis, and biological evaluation of novel pyrazole-phenylcarbamothioyl derivatives as multitarget antidiabetic agents:
AU - Madalambika
AU - A.C. Kumar
AU - P.M. BharathKumar
AU - J. Rangaswamy
AU - N. Akshaya Simha
AU - Ramith Ramu
AU - Nagaraja Naik
PY - 2026
DA - 2026/10/30
JO - Results in Chemistry
DO - 10.1016/j.rechem.2026.103998
UR - https://doi.org/10.1016/j.rechem.2026.103998
AB - 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 μM 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 μM , compared with acarbose (120.23 ± 1.2 μM). Compound 5j demonstrated the strongest aldose reductase inhibition ( IC 50 = 15.32 ± 0.94 μM ), 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 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.
SN - 2211-7156
ER -