New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies (original) (raw)
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Bioorganic chemistry, 2018
α-Glucosidase is a catabolic enzyme that regulates the body's plasma glucose levels by providing energy sources to maintain healthy functioning. 2-Amino-thiadiazole (1-13) and 2-amino-thiadiazole based Schiff bases (14-22) were synthesized, characterized byH NMR and HREI-MS and screened for α-glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied degree of α-glucosidase inhibitory potential with ICvalues ranging between 2.30 ± 0.1 to 38.30 ± 0.7 μM, when compare with standard drug acarbose having ICvalue of 39.60 ± 0.70 μM. Among the series eight derivatives 1, 2, 6, 7, 14, 17, 19 and 20 showed outstanding α-glucosidase inhibitory potential with ICvalues of 3.30 ± 0.1, 5.80 ± 0.2, 2.30 ± 0.1, 2.70 ± 0.1, 2.30 ± 0.1, 5.50 ± 0.1, 4.70 ± 0.2, and 5.50 ± 0.2 μM respectively, which is many fold better than the standard drug acarbose. The remaining analogs showed good to excellent α-glucosidase inhibition. Structure activity relationship has been established for a...
Bioorganic Chemistry, 2016
A novel series of chromone-isatin derivatives 6a-6p were designed, synthesized and characterized by 1 H NMR, 13 C NMR and HRMS. These novel synthetic compounds were evaluated for inhibitory activity against yeast α-glucosidase enzyme. The results of biological test have shown that all tested compounds exhibited excellent to potent inhibitory activity in the range of IC 50 = 3.18 ± 0.12-16.59 ± 0.17 µM as compared to the standard drug acarbose (IC 50 = 817.38 ± 6.27 µM). Compound 6j (IC 50 = 3.18 ± 0.12 µM) with a hydroxyl group at the 7-position of chromone and a 4-bromobenzyl group at the N1-positions of isatin, was found to be the most active compound among the series. Furthermore, molecular docking study was performed to help understand binding interactions of the most active analogs with α-glucosidase enzyme. These results indicated that this class of compounds had potential for the development of anti-diabetic agents.
Bioorganic Chemistry
A series of thiazole derivatives 1-21 were prepared, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed good α-glucosidase inhibitory activity with IC50 value ranging between 18.23±0.03 and 424.41±0.94μM when compared with the standard acarbose (IC50, 38.25±0.12μM). Compound (8) (IC50, 18.23±0.03μM) and compound (7) (IC50=36.75±0.05μM) exhibited outstanding inhibitory potential much better than the standard acarbose (IC50, 38.25±0.12μM). All other analogs also showed good to moderate enzyme inhibition. Molecular docking studies were carried out in order to find the binding affinity of thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of α-glucosidase inhibitors. Copyright © 2015. Published by Elsevier Inc.
A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a−m provided access to the target 5-(arylideneamino)-1H-benzo[d]imidazole-2-thiols 7a−m. The results of the bioactivity assessment revealed all the compounds as excellent inhibitors of the enzyme (IC 50 range: 0.64 ± 0.05 μM to 343.10 ± 1.62 μM) than acarbose (873.34 ± 1.21). Among them, 7i was the most active inhibitor (IC 50 : 0.64 ± 0.05 μM) followed by 7d (
Diabetes is a leading cause of kidney failure, blindness, heart attacks and lower limb amputation. Prevalence of diabetes is rising globally. α-glucosidase is validated target for controlling hyperglycemia because of its role in catalysing hydrolysis of carbohydrates to glucose in GIT. In an attempt to find novel safe and effective α-glucosidase inhibitors, coumarin linked thiazole were identified as potential scaffold on the basis of their interactions with the active site of α-glucosidase studied in silico. A series of coumarin linked thiazole derivatives were synthesized and analysed for α-glucosidase inhibitory potential in an in-vitro assay. The synthesized molecules showed potent inhibition of α-glucosidase with IC50 values ranging from 0.14 to 9.38 μM. The most potent compound 2-((4-bromophenyl) amino)-N-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl) acetamide was further docked with α-glucosidase and molecular dynamics studies were carried out for 100ns which suggested the stabili...
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Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (7–21) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives 19 (IC50 = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and 20 (IC50 = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC50 = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representative...
Thiadiazole derivatives as New Class of β-glucuronidase inhibitors
Bioorganic & Medicinal Chemistry, 2016
Thiadiazole derivatives 1-24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC 50 = 2.16 ± 0.01-58.06 ± 1.60 µM as compare to standard D-saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 µM). Molecular docking study was conducted in order to establish the structure-activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques 1 H, 13 CNMR, and EIMS.
Bioorganic Chemistry, 2019
Twenty-five thiadiazole derivatives 1-25 were synthesized from methyl 4methoxybenzoate via hydrazide and thio-hydrazide intermediates, and evaluated for their potential against β-glucuronidase enzyme. Most of the compounds including 1 (IC 50 = 26.05 ± 0.60 μM), 2 (IC 50 = 42.53 ± 0.80 μM), 4 (IC 50 = 38.74 ± 0.70 μM), 5 (IC 50 = 9.30 ± 0.29 μM), 6 (IC 50 = 6.74 ± 0.26 μM), 7 (IC 50 = 18.40 ± 0.66 μM), and 15 (IC 50 = 18.10 ± 0.53 μM) exhibited superior activity potential than the standard D-saccharic acid-1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interaction with enzyme active site.
Journal of Molecular Structure, 2023
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Synthesis, in-vitro α-glucosidase inhibition, antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2,5-dione and thiazolidine-2,4-dione derivatives
Molecular Diversity, 2021
A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC 50 values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC 50 = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor.