scholarly journals Glucose oxidase as a model enzyme for antidiabetic activity evaluation of medicinal plants: In vitro and in silico evidence

2022 ◽  
Author(s):  
Colette Ashande ◽  
Adrien Masunda ◽  
Koto-te-Nyiwa Ngbolua ◽  
Jason Thambwe Kilembe ◽  
Aristote Matondo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Hydrogen Bonds ◽  
Glucose Oxidase ◽  
Antidiabetic Activity ◽  
Stable Complex ◽  
Marker Enzyme ◽  
Activity Evaluation ◽  
Uv Visible

Diabetes mellitus is a major public health problem in the world. In Africa, more than 80% of patients use plants for their treatment. However, the methods of validation of endogenous knowledge usually used are costly. The alternative method developed in this study aims at creating hyperglycemia <i>in vitro</i> and exploiting the metabolic pathway involving glucose oxidase for UV-visible spectrophotometric screening of medicinal plants’ antidiabetic activity. The evolution of glucose oxidation as a function of drug concentration is followed by UV-visible spectrophotometry. The formation of the stable complex between the enzyme and the inhibitor is studied using molecular docking. Drugs used (Gliben) and plant extracts exhibited an <i>in vitro</i> hypoglycemic effect by reducing exponentially, <i>in vitro</i>, the level of free glucose. The results also showed that <i>L. multiflora</i> is more active than <i>V. amygdalina</i> (IC<sub>50</sub>: 1.36 ± 0.09 mg/mL Vs IC<sub>50</sub>: 3.00 ± 0.54 mg/mL). Gliben (0.5 mg/mL) and <i>L. multiflora</i> (2 mg/mL) reduced both the rate of oxidation of glucose by glucose oxidase (catalytic power V<sub>max</sub>: 0.84 ± 0.11 mg*mL<sup>-1</sup>*min<sup>-1</sup> for Gliben and 1.72 ± 0.13 mg*mL<sup>-1</sup>*min<sup>-1</sup> for <sup>L. multiflora</sup>); and the affinity of this enzyme for its substrate-glucose (K<sub>M</sub>: 15.11 ± 2.72 mg*mL<sup>-1</sup> for Gliben and 9.17 ± 1.56 mg*mL<sup>-1</sup> for <i>L. multiflora</i>) when these results are compared to enzyme catalysis in the absence of inhibitor (V<sub>max</sub>: 2.86 ± 0.44 mg*mL<sup>-1</sup>*min-1; K<sub>M</sub>: 8.07 ± 1.96 mg*mL<sup>-1</sup>). The binding of GOX (1GAL) to selected phytocompounds derived from <i>L. multiflora</i> was confirmed by molecular docking. The most stable complexes were obtained for four compounds; <b>8</b> (-10.1±0.0 Kcal/mol), <b>6</b> (-9.5±0.1 Kcal/mol), <b>3</b> (-8.3±0.0 Kcal/mol) and <b>9</b> (-8.2±0.1 Kcal/mol). Among these, compounds <b>8</b> and <b>6</b> formed complexes with the enzyme stabilized by hydrogen bonds, the compound <b>8</b> forms 5 hydrogen bonds (<b>ASN514</b>, <b>ASP424</b>, <b>ARG95</b>, <b>TYP68</b>, <b>LEU65</b>) while compound <b>6</b> forms 2 hydrogen bonds (<b>ASN514</b> and <b>SER422</b>). However, no H-bonding interaction occurs in the complex that involves ligands <b>9</b> and <b>3</b> despite their high binding energy (-8.2±0.1 Kcal/mol and -8.3±0.0 Kcal/mol respectively). Glucose oxidase can serve as a marker enzyme for<i> in vitro</i> antidiabetic activity evaluation of medicinal plants.

scholarly journals Antioxidant and α-Glucosidase Inhibitory Activities of Fisetin

2018 ◽  
Vol 13 (11) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Yike Yue ◽  
Yongsheng Chen ◽  
Sheng Geng ◽  
Guizhao Liang ◽  
Benguo Liu
Keyword(s):  
Antioxidant Activity ◽  
Molecular Docking ◽  
Medicinal Plants ◽  
Hydrogen Bonds ◽  
Competitive Inhibition ◽  
Radical Scavenging ◽  
Docking Analysis ◽  
Inhibitory Activities ◽  
Molecular Docking Analysis

Fisetin is a flavonoid widespread in vegetables, fruits and medicinal plants. The in vitro antioxidant and α-glucosidase inhibitory activities of fisetin were systemically investigated in this study. The DPPH and ABTS radical scavenging performance of fisetin was higher than that of BHA. In the ORAC and PSC assays, fisetin also exhibited strong antioxidant activity. The α-glucosidase inhibitory activity of fisetin (IC50, 9.38±0.35 μg/mL) was significantly superior to that of acarbose (IC50, 1.07±0.15 mg/mL). Its inhibition type was determined to be a mixed competitive and non-competitive inhibition mode. Molecular docking analysis suggested it could exert the α-glucosidase inhibitory role by forming hydrogen bonds with the TRP391, ASP392, ARG428 and ASP568 residues of α-glucosidase.

scholarly journals Characterization of Possible α-Glucosidase Inhibitors from Trigonella stellata Extract Using LC–MS and In Silico Molecular Docking

Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 208
Author(s):  
Ahlam Elwekeel ◽  
Dalia El Amir ◽  
Enas I. A. Mohamed ◽  
Elham Amin ◽  
Marwa H. A. Hassan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Flavonoid Glycosides ◽  
Total Phenolic ◽  
Cytotoxic Activities ◽  
Alcoholic Extract ◽  
Molecular Docking Study

The current study accentuates the significance of performing the multiplex approach of LC-HRESIMS, biological activity, and docking studies in drug discovery, taking into consideration a review of the literature. In this regard, the investigation of antioxidant and cytotoxic activities of Trigonella stellata collected from the Egyptian desert revealed a significant antioxidant capacity using DPPH with IC50 = 656.9 µg/mL and a moderate cytotoxicity against HepG2, MCF7, and CACO2, with IC50 values of 53.3, 48.3, and 55.8 µg/mL, respectively. The evaluation of total phenolic and flavonoid contents resulted in 32.8 mg GAE/g calculated as gallic acid equivalent and 5.6 mg RE/g calculated as rutin equivalent, respectively. Chemical profiling of T. stellata extract, using LC-HRESIMS analysis, revealed the presence of 15 metabolites, among which eleven compounds were detected for the first time in this species. Interestingly, in vitro testing of the antidiabetic activity of the alcoholic extract noted an α-glucosidase enzyme inhibitory activity (IC50 = 559.4 µg/mL) better than that of the standard Acarbose (IC50 = 799.9 µg/mL), in addition to a moderate inhibition of the α-amylase enzyme (IC50 = 0.77 µg/mL) compared to Acarbose (IC50 = 0.21 µg/mL). α-Glucosidase inhibition was also virtualized by binding interactions through the molecular docking study, presenting a high binding activity of six flavonoid glycosides, as well as the diterpenoid compound graecumoside A and the alkaloid fenugreekine. Taken together, the conglomeration of LC-HRESIMS, antidiabetic activity, and molecular docking studies shed light on T. stellata as a promising antidiabetic herb.

scholarly journals Rationale design and synthesis of some novel imidazole linked thiazolidinone hybrid molecules as DNA minor groove binders

2020 ◽  
Vol 11 (2) ◽  
pp. 120-132
Author(s):  
Javeed Ahmad War ◽  
Santosh Kumar Srivastava
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Specific Binding ◽  
Minor Groove ◽  
Stable Complex ◽  
Binding Studies ◽  
In Vitro Susceptibility ◽  
Reference Drug ◽  
Hybrid Molecules

A new series of imidazole linked thiazolidinone hybrid molecules was designed and subsequently synthesized through a feasible, three step reaction protocol. The structures of these molecules were established using FT-IR, 1H NMR, 13C NMR and HRMS techniques. In vitro susceptibility tests against some Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa) exhibited broad spectrum potency of the molecules. The most potent molecule (S2A7) amongst the screened molecules, showed minimum inhibitory concentration (MIC) value not less than 2.0 µg/mL which was at par with the reference drug Streptomycin. Structure activity relationships revealed nitro and chloro groups being crucial for bioactivity when present at meta position of arylidene ring in 3-(3-(imidazol-1-yl)propyl)-5-(benzylidene)-2-(phenylimino)thiazolidin-4-one. Deoxyribonucleic acid (DNA)and bovine serum albumin (BSA) binding studies for S2A7 under simulated physiological pH were probed using UV-Visible, fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that S2A7 has strong binding affinity towards DNA and binds at the minor groove of DNA with binding constant (Kb) of 0.1287×102 L/mol. Molecular docking simulations of S2A7 with DNA and BSA predicted binding affinity of -9.2 and -7.2 kcal/mol, respectively. Van der Waals forces and hydrogen bonding interactions were predicted as the main forces of interaction. With DNA, S2A7 exhibited specific binding affinity towards adenine-thiamine base pairs. The compound S2A7 forms a stable complex with BSA by binding at subdomain IIIA implying high bio-distribution of the compound.

scholarly journals Structural Basis of Binding and Rationale for the Potent Urease Inhibitory Activity of Biscoumarins

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Muhammad Arif Lodhi ◽  
Sulaiman Shams ◽  
Muhammad Iqbal Choudhary ◽  
Atif Lodhi ◽  
Zaheer Ul-Haq ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Docking Simulation ◽  
Cysteine Residue ◽  
Structural Basis ◽  
Bacillus Pasteurii ◽  
Nickel Ions ◽  
Jack Bean ◽  
Uv Visible

Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins1–10for their mechanisms of inhibition with the nickel containing active sites of Jack bean andBacillus pasteuriiureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case ofBacillus pasteuriiurease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.

Discovery of potential inhibitors of the receptor-binding domain (RBD) of pandemic disease-causing SARS-CoV-2 Spike Glycoprotein from Triphala through molecular docking

2021 ◽  
Vol 01 ◽  
Author(s):  
Sharuk L. Khan ◽  
Falak A. Siddiqui ◽  
Mohd Sayeed Shaikh ◽  
Nitin V. Nema ◽  
Aijaz A. Shaikh
Keyword(s):  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Receptor Binding ◽  
Chemical Constituents ◽  
Antioxidant Properties ◽  
Binding Domain ◽  
Quality Data ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein

Background: COVID-19 (SARS-CoV-2 infection) has affected almost every region of the world. Presently, there is no defined line of treatment available for it. Triphala is already proven to have a safe biological window and well known for its antioxidant and immunomodulatory properties. Objective: Present work has been carried out to study Triphala's effectiveness for the treatment of COVID-19. Methods: The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein responsible for the invasion into the host cell, which leads to further infection. The molecular docking (MD) was performed to explore the binding affinities (kcal/mol) of Triphala's chemical constituents and compared them with the existing drugs under investigation for the treatment of COVID-19 epidemiology. Results: Chebulinic acid binding affinity -8.5 kcal/mol with the formation of 10 hydrogen bonds. Almost all the major chemical constituents have formed two or more hydrogen bonds with RBD of SARS-CoV-2 Spike Glycoprotein. Conclusion: The present study showed that Triphala might perform vital roles in the treatment of COVID-19 and expand its usefulness to physicians to treat this illness. There is a need to complete the in-vitro, in-vivo biological testing of Triphala on SARS-CoV-2 disease to create more quality data. The binding mode of Chebulinic acid in the allosteric cavity allows a better understanding of RBD of SARS-CoV-2 Spike Glycoprotein target and provides insight for the design of new inhibitors. Triphala is already proven to have a safe biological window, which indicates we can skip the pre-clinical trials. Apart from this, Triphala is well known for its antioxidant properties, which ultimately improves the immunity of the COVID-19 patient.

Novel Pyrazolo[3,4‐ d ]pyrimidine‐Containing Amide Derivatives: Synthesis, Molecular Docking, In Vitro and In Vivo Antidiabetic Activity

2019 ◽  
Vol 4 (34) ◽  
pp. 10072-10078
Author(s):  
Bijivemula N. Reddy ◽  
Radhakrishnam Raju. Ruddarraju ◽  
Gangarapu. Kiran ◽  
Madhvesh Pathak ◽  
Anreddy Rama Narsimha Reddy
Keyword(s):  
Molecular Docking ◽  
Antidiabetic Activity ◽  
Amide Derivatives

scholarly journals PHARMACOLOGICAL EVALUATION OF FICUS RELIGIOSA FOR THEIR INVITRO HYPOGLYCEMIC ACTIVITY

2020 ◽  
pp. 1-2
Author(s):  
Poonam Pandey
Keyword(s):  
Diabetes Mellitus ◽  
Medicinal Plants ◽  
Metabolic Disorder ◽  
Antidiabetic Activity ◽  
Important Criterion ◽  
Ficus Religiosa ◽  
In Vitro Techniques ◽  
Pharmacological Evaluation ◽  
Disease Present

Diabetes mellitus is a metabolic disorder and its management is an important criterion for pharmacotherapy. The medicinal plants play very important role in preventing the progress of the disease. Present study deals with screening of polyherbal extracts using in-vitro techniques for its antidiabetic activity. The plants used in the present study are Ficus religiosa which use traditionally for the treatment of various ailments. In the present study different part of F. religiosa bark showed highest antioxidant and highest antidiabetic activity. This study indicates the curative beneƒOts of F. religiosa in traditional medicinal system.

scholarly journals Identification of 1, 2, 4-triazine and its derivatives against Lanosterol 14 - demethylase (CYP51) property of Candida albicans: Influence on the development of new antifungal therapeutic strategies

2021 ◽  
Author(s):  
Abhishek Kumar Verma ◽  
Aarfah Majid ◽  
Md. Shahadat Hossain ◽  
Sk. Faisal Ahmed ◽  
Mohammad Ashid ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Antifungal Drugs ◽  
Binding Affinities ◽  
Modern Drug ◽  
Low Toxicity ◽  
Derivatives Of ◽  
High Binding Affinity

This research aims to find out whether the synthetic 1, 2, 4-triazine and its derivatives have antifungal effects and can protect humans from infection with Candida albicans. Molecular docking and molecular dynamic simulation are widely used in modern drug design to target a We are interested in using molecular docking and molecular dynamics modelling to investigate the interaction between the derivatives of 1, 2, 4-triazine and the resulting lanosterol 14 - demethylase (CYP51) of Candida albicans The inhibition of Candida albicans CYP51 is the main goal of our research. The 1, 2, 4-triazine and its derivatives have been docked to the CYP51 enzyme, which is involved in Candida albicans Multidrug Drug Resistance (MDR). Autodock tools were used to identifying the binding affinities of molecules against the target proteins. Compared to conventional fluconazole, the molecular docking results indicated that each drug has a high binding affinity for CYP51 proteins and forms unbound interactions and hydrogen bonds with their active residues and surrounding allosteric residues. The docking contacts were made using a 10 ns MD simulation with nine molecules. RMSD, RMSF, hydrogen bonds, and the Rg all confirm these conclusions. In addition, these compounds were expected to have a favorable pharmacological profile and low toxicity. The compounds are being offered as scaffolds for the development of new antifungal drugs and as candidates for future in vitro testing.

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