A new entry into the portfolio of α-glucosidase inhibitors as potent therapeutics for type 2 diabetes: Design, bioevaluation and one-pot multi-component synthesis of diamine-bridged coumarinyl oxadiazole conjugates

2018 ◽  
Vol 77 ◽  
pp. 190-202 ◽  
Author(s):  
Madiha Kazmi ◽  
Sumera Zaib ◽  
Aliya Ibrar ◽  
Sayyeda Tayyeba Amjad ◽  
Zainab Shafique ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
One Pot ◽  
Glucosidase Inhibitors ◽  
New Entry

Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update

2019 ◽  
Vol 25 (23) ◽  
pp. 2510-2525 ◽  
Author(s):  
Bashir Usman ◽  
Neha Sharma ◽  
Saurabh Satija ◽  
Meenu Mehta ◽  
Manish Vyas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Patient Compliance ◽  
Postprandial Hyperglycemia ◽  
Diabetic Patients ◽  
Poor Patient ◽  
Glucosidase Inhibitors ◽  
Poor Patient Compliance ◽  
Recent Developments ◽  
Alpha Glucosidase

The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety. Alphaglucosidase is a family of enzyme originated from the pancreas which plays a role in the anabolism of 80-90% of carbohydrate consumed into glucose. This glucose is absorbed into the blood and results in frank postprandial hyperglycemia and worsens the conditions of diabetic patients which precipitate complications. Inhibition of these enzymes helps to prevent postprandial hyperglycemia and the formation of glycated end products. Alphaglucosidase inhibitors are reported to be more important in adequate control of type 2, but marketed drugs have various side effects, such as poor patient compliance and also expensive. This proves the needs for other class of drugs with better efficacy, safety, patient compliance and economic. In this review, we have emphasized the recent advances in the field of new alpha-glucosidase inhibitors with improved safety and pharmacological profile.

Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

2020 ◽  
Vol 16 ◽  
Author(s):  
Marjan Mollazadeh ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Yousef Valizadeh ◽  
Afsaneh Zonouzi ◽  
Mohammad Ali Faramarzi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kinetic Study ◽  
Active Site ◽  
Docking Study ◽  
Secondary Amines ◽  
Molecular Docking Study ◽  
Glucosidase Inhibitors ◽  
Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

scholarly journals Alpha-glucosidase inhibitors for type 2 diabetes mellitus

2002 ◽  
Author(s):  
F Van de Laar ◽  
S Wang ◽  
P Lucassen ◽  
E Van de Lisdonk ◽  
H Van den Hoogen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucosidase Inhibitors ◽  
Alpha Glucosidase

scholarly journals  -Glucosidase Inhibitors for Patients With Type 2 Diabetes: Results from a Cochrane systematic review and meta-analysis

Diabetes Care ◽  
2004 ◽  
Vol 28 (1) ◽  
pp. 154-163 ◽  
Author(s):  
F. A. van de Laar ◽  
P. L. Lucassen ◽  
R. P. Akkermans ◽  
E. H. van de Lisdonk ◽  
G. E. Rutten ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Cochrane Systematic Review ◽  
Glucosidase Inhibitors

scholarly journals Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ruth L. Coleman ◽  
Charles A. B. Scott ◽  
Zhihui Lang ◽  
M. Angelyn Bethel ◽  
Jaakko Tuomilehto ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Random Effects Models ◽  
Incident Type ◽  
Glucosidase Inhibitors ◽  
Incident Type 2 Diabetes ◽  
Cv Disease ◽  
The Impact ◽  
Alpha Glucosidase

Abstract Background Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. Methods We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. Results Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67–0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89–1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. Conclusions Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.

scholarly journals Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Longhao Zhang ◽  
Qiyan Chen ◽  
Ling Li ◽  
Joey S. W. Kwong ◽  
Pengli Jia ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Glucosidase Inhibitors ◽  
Alpha Glucosidase
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