Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking

2019 ◽  
Vol 10 (4) ◽  
pp. 1893-1902 ◽  
Author(s):  
Zi-wan Ning ◽  
Li-xiang Zhai ◽  
Tao Huang ◽  
Jiao Peng ◽  
Die Hu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Homology Model ◽  
Tea Leaves ◽  
Cyclocarya Paliurus ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities ◽  
Tof Ms

11 potential α-glucosidase inhibitors in leaves of Cyclocarya paliurus were quickly identified by UF-UPLC-Q/TOF-MS/MS, and their inhibitory activities were verified in vitro and in vivo, as well as docked with homology model.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

scholarly journals Cyclocarya paliurus tea leaves enhances pancreatic β cell preservation through inhibition of apoptosis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hai-tao Xiao ◽  
Bo Wen ◽  
Zi-wan Ning ◽  
Li-xiang Zhai ◽  
Cheng-hui Liao ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Pancreatic Β Cell ◽  
Diabetic Mice ◽  
Tea Leaves ◽  
Β Cell ◽  
Cyclocarya Paliurus ◽  
Obesity And Diabetes ◽  
Cell Preservation

Abstract Leaves of Cyclocarya paliurus are a sweet tea traditionally used to treat obesity and diabetes in China. However, its protective mechanisms against hyperglycemia remains unclear. Here, we demonstrate that the extract of C. paliurus leaves significantly decreased body loss, food intake and blood glucose level, and increased blood insulin level, β-cell number and insulin-producing β cells in high-fat diet-low dose STZ-induced diabetic mice. In vivo and in vitro studies also showed the extract of C. paliurus leaves significantly inhibited pancreatic β cell apoptosis by suppressing the expression of caspase 8, caspase 9 and cleaved caspase-3, as well as Bax/Bcl-2 ratio, down-regulating p38, ERK and JNK phosphorylation, and up-regulating Akt phosphorylation. These effects were significantly enhanced by inhibitor p-38 or ERK or JNK, and counteracted by inhibitor of PI3K. In addition, the extract of C. paliurus leaves also significantly improved hepatic steatosis, nephropathy and cardiac hypertrophy of diabetic mice. Taken together, these results provide the insight into the effects of C. paliurus leaves on pancreatic β cell preservation in standing glucolipotoxicity. Therefore, C. paliurus tea leaves may be used as a new remedy for diabetes through enhancing pancreatic β cell preservation by inhibiting β cell apoptosis.

Study on the interaction of 1,5-diaryl pyrrole derivatives with α-glucosidase; synthesis, molecular docking, and kinetic study

2019 ◽  
Vol 15 ◽  
Author(s):  
Tadesse Bekele Tafesse ◽  
Ebrahim Saeedian Moghadam ◽  
Mohammed Hussen Bule ◽  
Mohammad Ali Faramarzi ◽  
Mohammad Abdollahi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kinetic Studies ◽  
Postprandial Hyperglycemia ◽  
Binding Energies ◽  
Potential Candidate ◽  
Pyrrole Derivatives ◽  
Standard Drug ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

Background: The delaying of absorption of glucose is one of the principal therapeutic approaches of type 2 diabetes. α-glucosidase inhibitors compete with the α-glucosidase enzyme activity, which helps to reduce the conversion of carbohydrates into glucose and thereby control the postprandial hyperglycemia incidence. Objective: The aim of this study was to synthesize a series of novel 1,5-diphenyl pyrrole derivatives and evaluate their in vitro α-glucosidase inhibitory activities. Methods: Compounds were synthesized through a multistep reaction and were evaluated for α-glucosidase inhibitory activities. Molecular docking and kinetic studies were carried out to predict the mode of binding and mechanism of inhibition for the most active compounds, 5g and 5b, against α-glucosidase. Results: Synthesized compounds showed good in vitro α-glucosidase inhibitory activity with IC50 values in the range of (117.5 ± 3.8 to 426.0 ± 10.2 µM) as compared to acarbose, the standard drug, (750 ± 8.7 µM). Compound 5g (117.5 ± 3.8 µM) ascertained as the most potent inhibitor of α-glucosidase in a competitive mode. The binding energies of compounds 5g and 5b (119.0 ± 7.5 µM), as observed from the best docking conformations, indicates that they have a lower free binding energy (-3.26 kcal/mol and -3.0 kcal/mol, respectively) than acarbose (2.47 kcal/mol). Conclusion: The results of our study reveal that the synthesized compounds are a potential candidate for α-glucosidase inhibitors for the management of postprandial hyperglycemia for further investigation.

scholarly journals Molecular Docking of Isolated Alkaloids for Possible α-Glucosidase Inhibition

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 544 ◽  
Author(s):  
Rahman ◽  
Muhammad ◽  
Gul-E-Nayab ◽  
Khan ◽  
Aschner ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Digestive Enzyme ◽  
3D Structure ◽  
Target Protein ◽  
Binding Modes ◽  
Active Site Residues ◽  
Glucosidase Inhibitors

Diabetes mellitus, one of the most common endocrine-metabolic disorders, has caused significant morbidity and mortality worldwide. To avoid sugar digestion and postprandial hyperglycemia, it is necessary to inhibit α-glucosidase, a digestive enzyme with an important role in carbohydrate digestion. The criteria for the selection of alkaloids are based on their in vitro and in vivo activities on glucose modulation. The current study assessed the bonding potential of isolated alkaloids with the targeted protein. For this purpose, the 3D structure of the target protein (α-glucosidase) was reproduced using MODELLER 9.20. The modeled 3D structure was then validated and confirmed by using the RAMPAGE, ERRAT, and Verify3D online servers. The molecular docking of 32 alkaloids reported as α-glucosidase inhibitors, along with reference compounds (acarbose and miglitol), was done through MOE-Dock applied in MOE software to predict the binding modes of these drug-like compounds. The results revealed that nummularine-R and vindoline possess striking interactions with active site residues of the target protein, and were analogous to reference ligands. In conclusion, the current study provided a computational background to the α-glucosidase inhibitors tested. This novel information should facilitate the development of new and effective therapeutic compounds for the treatment of diabetes mellitus.

Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

2019 ◽  
Vol 16 (6) ◽  
pp. 696-710
Author(s):  
Mahmoud Balbaa ◽  
Doaa Awad ◽  
Ahmad Abd Elaal ◽  
Shimaa Mahsoub ◽  
Mayssaa Moharram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Active Sites ◽  
Biological Activities ◽  
Imidazole Ring ◽  
Quantitative Structure Activity Relationship ◽  
Binding Interaction ◽  
Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

Synthesis and molecular docking of hybrids ionic azole Schiff bases as novel CDK1 inhibitors and anti-breast cancer agents: in vitro and in vivo study

2021 ◽  
pp. 131041
Author(s):  
Waleed M. Serag ◽  
Faten Zahran ◽  
Yasmin M. Abdelghany ◽  
Reda F.M. Elshaarawy ◽  
Moustafa S. Abdelhamid
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Schiff Bases ◽  
In Vivo Study

scholarly journals In VivoEfficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization

2015 ◽  
Vol 59 (4) ◽  
pp. 2113-2121 ◽  
Author(s):  
U. Malik ◽  
O. N. Silva ◽  
I. C. M. Fensterseifer ◽  
L. Y. Chan ◽  
R. J. Clark ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Sequence Similarity ◽  
Infection Model ◽  
Content Type ◽  
Wide Range ◽  
Inhibitory Activities ◽  
The Impact

ABSTRACTStaphylococcus aureusis a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weakin vitroinhibitory activities againstS. aureus, but several had strong antibacterial activities againstS. aureusin anin vivomurine wound infection model. pYR, an immunomodulatory peptide fromRana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg−1. Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

scholarly journals Synthetic spirocyclic endoperoxides: new antimalarial scaffolds

MedChemComm ◽  
2015 ◽  
Vol 6 (2) ◽  
pp. 357-362 ◽  
Author(s):  
Margherita Brindisi ◽  
Sandra Gemma ◽  
Sanil Kunjir ◽  
Luisa Di Cerbo ◽  
Simone Brogi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimalarial Activity ◽  
Design Synthesis ◽  
Docking Calculation

Design, synthesis and molecular docking calculation studies led to the identification of novel spirocyclic peroxides with in vitro and in vivo antimalarial activity.

scholarly journals Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

2018 ◽  
Vol 13 (2) ◽  
pp. 149 ◽  
Author(s):  
Naureen Shehzadi ◽  
Khalid Hussain ◽  
Nadeem Irfan Bukhari ◽  
Muhammad Islam ◽  
Muhammad Tanveer Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Video Clip ◽  
Serum Levels ◽  
Docking Studies ◽  
Normal Serum ◽  
Yeast Cells ◽  
Drug Candidate ◽  
Molecular Docking Studies

<p class="Abstract">The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta<sub>2</sub>-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.</p><p class="Abstract"><strong>Video Clip of Methodology:</strong></p><p class="Abstract">Glucose uptake by yeast cells:   4 min 51 sec   <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a>   <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a></p>

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