scholarly journals Structure-Activity Relationships ofN-Cinnamoyl and Hydroxycinnamoyl Amides onα-Glucosidase Inhibition

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Maya G. Chochkova ◽  
Petranka P. Petrova ◽  
Boyka M. Stoykova ◽  
Galya I. Ivanova ◽  
Martin Štícha ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cinnamic Acid ◽  
Inhibitory Activity ◽  
Diabetes Mellitus Type 2 ◽  
Significant Inhibition ◽  
Cinnamic Acid Derivatives ◽  
Structure Activity ◽  
Glucosidase Inhibitors

Currently, there is an increasing interest towardsα-glucosidase inhibition of various diseases including diabetes mellitus type 2, cancer, HIV, and B- and C-type viral hepatitis. Cinnamic acid derivatives have been shown to be potentially valuable as a new group ofα-glucosidase inhibitors. Therefore, herein, theα-glucosidase inhibitory activity oftrans-N-cinnamoyl and hydroxycinnamoyl amides was studied in vitro. Results revealed that the tested hydroxycinnamoyl amides (1–16) inhibiteda-glucosidase with IC50s ranging between 0.76 and 355.1 μg/ml. Compounds1,2,5,6,9,14, and15showed significant inhibition of yeastα-glucosidase, being even more potent ones than the used positive inhibitor acarbose (IC50=2.50±0.21 μg/ml).

Targeting α -(1,4)-Glucosidase in Diabetes Mellitus Type 2: The Role of New Synthetic Coumarins as Potent Inhibitors

2019 ◽  
Vol 18 (27) ◽  
pp. 2327-2337
Author(s):  
Catalina Figueroa-Benavides ◽  
Maria João Matos ◽  
Montserrat Peñaloza-Amion ◽  
Rubén Veas ◽  
Gabriela Valenzuela-Barra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Mellitus Type 2 ◽  
Hydrophobic Interactions ◽  
Docking Studies ◽  
Diabetes Mellitus Type ◽  
Glucosidase Inhibitors ◽  
Pharmacological Targets

Diabetes mellitus type 2 (DMT2) is a metabolic disease characterized by a chronic increase in glycemia that promotes several long-term complications and high mortality. Some enzymes involved in glycaemic control, such as α -(1,4)-glucosidase, have now been established as novel pharmacological targets. Coumarins have shown benefits in attenuating signs and complications of DMT2, including inhibition of this enzyme. In this work, new synthetic coumarins (bearing different amide and aryl substituents) were studied in vitro as inhibitors of α-(1,4)-glucosidase. Among them, five molecules proved to be excellent α-(1,4)-glucosidase inhibitors, being compound 7 (IC50 = 2.19 µM) about 200 times more potent than acarbose, a drug currently used for the treatment of DMT2. In addition, most of the coumarins presented uncompetitive inhibition for the α-(1,4)-glucosidase. Molecular docking studies revealed that coumarins bind to the active site of the enzyme in a more external area comparing to the substrate, without interfering with it, and displaying aromatic and hydrophobic interactions, as well as some hydrogen bonds. According to the results, aromatic interactions with two phenylalanine residues, 157 and 177, were the most common among the studied coumarins. This study is a step forward for the understanding of coumarins as potential anti-diabetic compounds displaying α-(1,4)-glucosidase inhibition.

2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management

2020 ◽  
Vol 16 (6) ◽  
pp. 826-840
Author(s):  
Saeed Ullah ◽  
Salma Mirza ◽  
Uzma Salar ◽  
Shafqat Hussain ◽  
Kulsoom Javaid ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inhibitory Activity ◽  
Kinetic Studies ◽  
Binding Pocket ◽  
Docking Studies ◽  
Standard Drug ◽  
Dual Nature ◽  
Benzothiazole Derivatives ◽  
Glucosidase Inhibitors

Background: Results of our previous studies on antiglycation activity, and the noncytotoxicity of 2-mercapto benzothiazoles, encouraged us to further widen our investigation towards the identification of leads against diabetes mellitus. Methods: 33 derivatives of 2-mercapto benzothiazoles 1-33 were evaluated for in vitro α- glucosidase inhibitory activity. Mode of inhibition was deduced by kinetic studies. To predict the interactions of 2-mercapto benzothiazole derivatives 1-33 with the binding pocket of α-glucosidase enzyme, molecular docking studies were performed on the selected inhibitors. Results: Compounds 2-4, 6-7, 9-26, 28 and 30 showed many folds potent α-glucosidase inhibitory activity in the range of IC50 = 31.21-208.63 μM, as compared to the standard drug acarbose (IC50 = 875.75 ± 2.08 μM). It was important to note that except derivative 28, all other derivatives were also found previously to have antiglycating potential in the range of IC50 = 187.12-707.21 μM. Conclusion: A number of compounds were identified as dual nature as antiglycating agent and α- glucosidase inhibitors. These compounds may serve as potential lead candidates for the management of diabetes mellitus.

scholarly journals Novel Metformin Analogues for Treatment of Pancreatic Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1027-A1028
Author(s):  
Lorena P Burton ◽  
Gang Deng ◽  
Cristian D Yanes ◽  
Jaydutt V Vadgama ◽  
Michael E Jung ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Tumor Progression ◽  
Clinical Benefit ◽  
Diabetes Mellitus Type 2 ◽  
Mtor Signaling ◽  
Diabetes Mellitus Type ◽  
Antitumor Effects ◽  
Incidence And Mortality

Abstract Pancreatic ductal adenocarcinoma (PDCA) is a leading cause of cancer death in the US. Patients diagnosed with PDCA generally present with advanced disease with poor prognosis and limited treatment options. African American patients have higher incidence and mortality of PDCA than Caucasian American or any other ethnic group. Different factors have been attributed to contribute to this health disparity, among them higher incidence of Diabetes Mellitus type 2. To address the need for new therapeutic approaches, we note epidemiologic reports that patients with diabetes mellitus-type 2 treated with the biguanide drug metformin, but not other antidiabetic drugs, have a reduced risk of PDCA and an increased survival rate among those with PDCA. The main physiologic effect of metformin is to lower blood glucose and reduce hyperinsulinemia associated with insulin resistance. In the cell, metformin stimulates AMP-activated protein kinase (AMPK) that in turn inhibits mTORC1 which integrates signals from an array of intracellular pathways to regulate cell growth. Recent clinical trials describe modest antiproliferative effects from use of neoadjuvant metformin, but no significant clinical benefit occurred when metformin was dosed at glycemic control levels in patients with advanced cancers. These findings suggest that development of more potent anticancer analogues of metformin may help to boost clinical benefit and patient survival. Hence, we have designed new biguanide analogues of metformin, and screening of these compounds in preclinical PDCA models show that selected analogues are more efficacious in blocking tumor progression than parental metformin at lower doses. Using proliferation assays in vitro, PDCA cells (Panc 1, MIA Paca-2) were treated 72-hrs with metformin or analogues, and greater dose-dependent inhibition of PDCA cell proliferation was found with analogues as compared to metformin (P<0.001). Further, apoptosis was also markedly induced by metformin analogues as compared to parental metformin (P<0.01). Antitumor effects of metformin are attributed in part to activation LKB1-AMPK pathways and downstream blockade of mTOR signaling, which is often increased in PDCA cells. Using PDCA cells treated in vitro with analogues for 24-hrs, we find that analogues induce AMPK phosphorylation and suppression of mTOR signaling, thus blocking protein synthesis and tumor proliferation. With an in vivo PANC 1 xenograft model in nude mice, lead metformin analogues given by oral gavage daily significantly inhibited tumor progression over 28-days as compared to appropriate controls (P<0.0001). Our findings show that selected metformin analogues have potent anticancer activity in preclinical PDCA models and may have promise as new targeted therapeutics for patients afflicted with this deadly disease. [Funded by NIH/NCI R21CA176337 and NIH/NCI U54 CA143930]

Analyzing Phytochemicals as Inhibitors of Diabetes Mellitus 2 Causing Proteins based on Computer-Aided Drug Discovery Protocols

2020 ◽  
Vol 10 ◽  
Author(s):  
Sobia Nazir Chaudry ◽  
Waqar Hussain ◽  
Nouman Rasool
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Diabetes Mellitus Type 2 ◽  
Multidrug Resistant ◽  
Diabetes Mellitus Type ◽  
In Vivo Studies ◽  
Fructose 1,6 Bisphosphate

Background: Diabetes Mellitus type 2 is one of the complex diseases, affecting people both in developed and developing countries. Plant extracted compounds known as phytochemicals are worthy because they have various medicinal properties. Objective: The present study aims at the in silico discovery of novel potent inhibitors against Diabetes Mellitus type 2. Methods: A total of 2750 phytochemicals from various medicinal important plants were collected for this study. Origin of these plants was Pakistan and India. The ADMET, molecular docking approaches were used to determine the binding and reactivity of these phytochemicals as Diabetes Mellitus type 2 inhibitors. Results: The ADMET analysis and molecular docking resulted in the selection of 42 phytochemicals (3 against Glucokinase receptor, 22 against Fructose 1,6 Bisphosphate protein and 17 for multidrug-resistant protein) showing high binding affinity as compared to the previously reported inhibitors of Diabetes Mellitus type 2. Conclusions: These 42 phytochemicals can be considered novel inhibitors against Diabetes Mellitus type 2 and can be selected for additional in vitro and in vivo studies to develop a suitable drug against diabetes.

scholarly journals Screening ofα-Glucosidase Inhibitory Activity from Some Plants of Apocynaceae, Clusiaceae, Euphorbiaceae, and Rubiaceae

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Berna Elya ◽  
Katrin Basah ◽  
Abdul Mun'im ◽  
Wulan Yuliastuti ◽  
Anastasia Bangun ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Spectrophotometric Methods ◽  
Type 2 Dm ◽  
Activity Test ◽  
Glucosidase Inhibitors ◽  
Ethanol Extracts ◽  
Sugar Levels ◽  
Global Health Problem

Diabetes mellitus (DM) is recognized as a serious global health problem that is characterized by high blood sugar levels. Type 2 DM is more common in diabetic populations. In this type of DM, inhibition ofα-glucosidase is a useful treatment to delay the absorption of glucose after meals. As a megabiodiversity country, Indonesia still has a lot of potential unexploited forests to be developed as a medicine source, including as theα-glucosidase inhibitor. In this study, we determine theα-glucosidase inhibitory activity of 80% ethanol extracts of leaves and twigs of some plants from the Apocynaceae, Clusiaceae, Euphorbiaceae, and Rubiaceae. Inhibitory activity test of theα-glucosidase was performedin vitrousing spectrophotometric methods. Compared with the control acarbose (IC50117.20 μg/mL), thirty-seven samples of forty-five were shown to be more potentα-glucosidase inhibitors with IC50values in the range 2.33–112.02 μg/mL.

scholarly journals IN VITRO ANTIDIABETIC EFFECTS OF FERULA ASSA-FOETIDA EXTRACTS THROUGH DIPEPTIDYL PEPTIDASE IV AND α-GLUCOSIDASE INHIBITORY ACTIVITY

2017 ◽  
Vol 10 (5) ◽  
pp. 357 ◽  
Author(s):  
Adel Yarizade ◽  
Hsan Hasani Kumle ◽  
Ali Niazi
Keyword(s):  
Diabetes Mellitus ◽  
Inhibitory Activity ◽  
Postprandial Glucose ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv ◽  
Glucosidase Inhibitors ◽  
Treatment Of Diabetes ◽  
Ethanol Ethanol

Objective: Diabetes mellitus (DM) causes hyperglycemia, which is one of the most common diseases in the world. One of the strategies for the treatment of diabetes is maintaining postprandial glucose level through inhibition of dipeptidyl peptidase IV (DPP-IV) and α-glucosidase enzymes. The aim of this study was to determine in vitro antidiabetic potential of Ferula assa-foetida via DPP-IV and α-glucosidase inhibitory activities.Methods: F. assa-foetida seeds were extracted in methanol, ethanol, ethanol-methanol, and water. Inhibitory activity on DPP-IV and α-glucosidase wasperformed in vitro and measured spectrophotometrically at λ=405 nm.Results: The result showed that the F. assa-foetida seed extract is effective against both enzymes. All fractions had DPP-IV inhibitory activity, but the ethanolic fraction had the highest inhibitory activity on DPP-IV enzyme and significantly decreased DPP-IV activity (24.5%). With respect to α-glucosidase inhibitory activity, the aqueous extract has the highest inhibitory activity (28%).Conclusion: According to the results of this study, F. assa-foetida contains DPP-IV and α-glucosidase inhibitors and could be a potential source for the discovery of active constituents as α-glucosidase and DPP-IV inhibitors to treat Type 2 DM.Keywords: Diabetes mellitus, Herbal medicine, Dipeptidyl peptidase IV, α-glucosidase.

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