scholarly journals Investigation of α-Glucosidase Inhibitory Metabolites from Tetracera scandens Leaves by GC–MS Metabolite Profiling and Docking Studies

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 287 ◽  
Author(s):  
Ahmed Nokhala ◽  
Mohammad Jamshed Siddiqui ◽  
Qamar Uddin Ahmed ◽  
Muhammad Safwan Ahamad Bustamam ◽  
Zainul Amiruddin Zakaria
Keyword(s):  
Metabolite Profiling ◽  
Docking Studies ◽  
Binding Energies ◽  
Antidiabetic Activity ◽  
Gas Chromatography Mass Spectrometry ◽  
Mass Spectral ◽  
Ic50 Values ◽  
Inhibitory Potential ◽  
Underlying Mechanisms

Stone leaf (Tetracera scandens) is a Southeast Asian medicinal plant that has been traditionally used for the management of diabetes mellitus. The underlying mechanisms of the antidiabetic activity have not been fully explored yet. Hence, this study aimed to evaluate the α-glucosidase inhibitory potential of the hydromethanolic extracts of T. scandens leaves and to characterize the metabolites responsible for such activity through gas chromatography–mass spectrometry (GC–MS) metabolomics. Crude hydromethanolic extracts of different strengths were prepared and in vitro assayed for α-glucosidase inhibition. GC–MS analysis was further carried out and the mass spectral data were correlated to the corresponding α-glucosidase inhibitory IC50 values via an orthogonal partial least squares (OPLS) model. The 100%, 80%, 60% and 40% methanol extracts displayed potent α-glucosidase inhibitory potentials. Moreover, the established model identified 16 metabolites to be responsible for the α-glucosidase inhibitory activity of T. scandens. The putative α-glucosidase inhibitory metabolites showed moderate to high affinities (binding energies of −5.9 to −9.8 kcal/mol) upon docking into the active site of Saccharomyces cerevisiae isomaltase. To sum up, an OPLS model was developed as a rapid method to characterize the α-glucosidase inhibitory metabolites existing in the hydromethanolic extracts of T. scandens leaves based on GC–MS metabolite profiling.

Mechanochemical Synthesis, in vitro Evaluation and Molecular Docking Studies of 4-Amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles as Antidiabetic Agents

2019 ◽  
Vol 16 (7) ◽  
pp. 560-568
Author(s):  
Vijayan R. Akhila ◽  
Maheswari R. Priya ◽  
Daisy R. Sherin ◽  
Girija K. Krishnapriya ◽  
Sreerekha V. Keerthi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Mechanochemical Synthesis ◽  
Active Sites ◽  
Docking Studies ◽  
Binding Energies ◽  
Antidiabetic Activity ◽  
Antidiabetic Agents ◽  
Molecular Docking Studies ◽  
Ic50 Value

The synthesis of 4-amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles 4a-h, as example of 2,4-diaminothiazole-benzofuran hybrids and an evaluation of their antidiabetic activity, by in vitro and computational methods, are reported. The synthesis of these diaminothiazoles was achieved mechano chemically by a rapid solvent-less method. Their antidiabetic activity was assessed by α-glucosidase and α-amylase inhibition assays. The, IC50 value for α-glucosidase inhibition by 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) was found to be 20.04 µM and the IC50 value for α-amylase inhibition, 195.03 µM, whereas the corresponding values for reference acarbose were 53.38 µM and 502.03 µM, respectively. Molecular docking studies at the active sites of α- glucosidase and α-amylase showed that among the diaminothiazoles 4a-h now studied, 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) has the highest D-scores of -8.63 and -8.08 for α-glucosidase and for α-amylase, with binding energies -47.76 and -19.73 kcal/mol, respectively.

scholarly journals Design, Synthesis and Biological Evaluation of Aromatase Inhibitors based on Sulfonates and Sulfonamides of Resveratrol

2021 ◽  
Vol 14 (10) ◽  
pp. 984
Author(s):  
Marialuigia Fantacuzzi ◽  
Marialucia Gallorini ◽  
Nicola Gambacorta ◽  
Alessandra Ammazzalorso ◽  
Zeineb Aturki ◽  
...  
Keyword(s):  
Aromatase Inhibitors ◽  
Biological Response ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Mcf7 Cell Line ◽  
Nano Liquid Chromatography ◽  
Inhibitory Potential

A library of sulfonate and sulfonamide derivatives of Resveratrol was synthesized and tested for its aromatase inhibitory potential. Interestingly, sulfonate derivatives were found to be more active than sulfonamide bioisosteres with IC50 values in the low micromolar range. The sulfonate analogues 1b–c and 1j exhibited good in vitro antiproliferative activity on the MCF7 cell line, evidenced by MTT and LDH release assays. Structure–activity relationships suggested that electronic and lipophilic properties could have a different role in promoting the biological response for sulfonates and sulfonamides, respectively. Docking studies disclosed the main interactions at a molecular level of detail behind the observed inhibition of the more active compounds whose chemical stability has been evaluated with nano-liquid chromatography. Finally, 1b–c and 1j were highlighted as sulfonates to be further developed as novel and original aromatase inhibitors.

scholarly journals SCREENING OF PHYTOCHEMICALS AND IN VITRO ANTIDIABETIC ACTIVITY OF BAUHINIA RACEMOSA LAM. LEAVES

2018 ◽  
Vol 11 (6) ◽  
pp. 190
Author(s):  
Bhimraj Gawade ◽  
Mazahar Farooqui
Keyword(s):  
Ethanol Extract ◽  
Mass Spectrometry Analysis ◽  
Antidiabetic Activity ◽  
Gas Chromatography Mass Spectrometry ◽  
Phytochemical Screening ◽  
Standard Drug ◽  
Spectrometry Analysis ◽  
Ic50 Value ◽  
Inhibitory Potential

Objective: In this study, the leaves of medicinal plant Bauhinia racemosa Lam. with different pharmacological activities were subjected to phytochemical screening and assessment of their in vitro inhibitory potential with porcine pancreatic α-amylase enzyme to treat and management of diabetes.Methods: Plant leaves were extracted sequentially with ethanol solvent. A modified 3,5-dinitrosalicylic acid method was adopted to screen α-amylase inhibition assay. The ethanol extract was analyzed qualitatively and gas chromatography–mass spectrometry analysis technique for the active phytoconstituents according to the standard protocols.Results: A phytochemical screening of leaves extract reveals the presence of carbohydrate, alkaloids, saponin, glycosides, steroids, tannins, flavonoids, triterpenoid, and phenolic compounds. The ethanol extract reported inhibition of α-amylase enzyme activity at IC50 value 61.72 ± 0.03 μg/mL and acarbose as a standard drug at IC50 value 28.07 ± 0.02 μg/mL.Conclusion: The results of the study indicate that B. racemosa Lam. leaves contain some of bioactive phytochemicals might to be exhibiting in vitro antidiabetic activity, which was leading to decreases the rate of starch digestion.

Screening chemical inhibitors for alpha-amylase from leaves extracts of Murraya koenigii (Linn.) and Aegle marmelos L.

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Alagar Yadav Sangilimuthu ◽  
Thirunavukkarasu Sivaraman ◽  
Rajkuberan Chandrasekaran ◽  
Karpagavalli Meenatchi Sundaram ◽  
Gayathiri Ekambaram
Keyword(s):  
Docking Studies ◽  
Alpha Amylase ◽  
Antidiabetic Activity ◽  
Gas Chromatography Mass Spectrometry ◽  
Murraya Koenigii ◽  
Aegle Marmelos ◽  
High Concentration ◽  
Low Concentrations ◽  
Chemical Inhibitors

AbstractObjectivesAqueous leaves extracts of Murraya koenigii (M. koenigii) and Aegle marmelos (A. marmelos) were prepared and effect of the extracts on inhibiting alpha-amylase playing essential roles on converting starch into glucose have been examined using in vitro assays.MethodsAlpha amylase inhibitory assay was used to asses the in vitro antidiabetic activity of the extracts. Gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify the volatile molecules of the extracts. Identified molecule were converted as ligand and docked against human pancreatic α-amylase (0.95 Å; PDB ID: 5U3A) using Autodock tool.ResultsThe data analyzes suggested that the alpha-amylase inhibition potential of the extract obtained from M. koenigii was stronger than that of the A. marmelos at low concentrations (<1 mg/mL), whereas both the extracts depicted similar inhibition effects on the enzyme at high concentration (>1 mg/mL). The phytochemicals present in both the plant extracts were identified by using their respective GC-MS data and the data analyzes revealed that the extracts of M. koenigii and A. Marmelos seemed to consist of about 20 and 24 diverse chemical molecules, respectively. Through the molecular docking studies, azulene of M. koenigii and hydroxycyclodecadiene of A. marmelos showed higher binding affinity on alpha-amylase.ConclusionsConcentration-dependent alpha-amylase inhibition effects of the extracts were observed and M. koenigii contains more alpha-amylase inhibitory effects due to the presence of azulene. This is primary lead to find out the better anti diabetic natural based drug to the society after clinical trial.

Novel Iodinated Hydrazide-hydrazones and their Analogues as Acetyl- and Butyrylcholinesterase Inhibitors

2020 ◽  
Vol 20 (23) ◽  
pp. 2106-2117
Author(s):  
Martin Krátký ◽  
Šárka Štěpánková ◽  
Michaela Brablíková ◽  
Katarína Svrčková ◽  
Markéta Švarcová ◽  
...  
Keyword(s):  
Biological Activities ◽  
Structural Parameters ◽  
Covalent Binding ◽  
Docking Studies ◽  
Potent Inhibition ◽  
Brain Barrier Permeability ◽  
Electric Eel ◽  
Ic50 Values ◽  
Ellman’S Method

Background: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias’ treatment. Objective: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. Methods: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman’s method. We calculated also physicochemical and structural parameters for CNS delivery. Results: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. Conclusion: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

scholarly journals The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 873
Author(s):  
Raphael J. Eberle ◽  
Danilo S. Olivier ◽  
Marcos S. Amaral ◽  
Ian Gering ◽  
Dieter Willbold ◽  
...  
Keyword(s):  
Binding Mode ◽  
Drug Candidates ◽  
Main Protease ◽  
Ic50 Values ◽  
Repurposed Drugs ◽  
Antiparasitic Drugs ◽  
Inhibitory Potential ◽  
Dynamics Simulations ◽  
Micromolar Range

Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

scholarly journals In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice

2018 ◽  
Vol 7 (9) ◽  
pp. 283 ◽  
Author(s):  
Sherif Hassan ◽  
Kateřina Berchová-Bímová ◽  
Miroslava Šudomová ◽  
Milan Malaník ◽  
Karel Šmejkal ◽  
...  
Keyword(s):  
Gas Chromatography ◽  
Clinical Practice ◽  
Essential Oil ◽  
Biological Activities ◽  
Structural Parameters ◽  
Antihypertensive Agents ◽  
Gas Chromatography Mass Spectrometry ◽  
Ic50 Values ◽  
Main Component

Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive (through inhibition of human angiotensin-converting enzyme; ACE) properties. The phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame-Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). In this study, all biological methods were performed at the level of in vitro studies. The results showed that TB-EO exerted remarked cytotoxic properties against human cervical carcinoma cells, colon cancer cells, and lung adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values of 7.22, 9.30, and 8.62 µg/mL, respectively, in comparison with that of standard anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 µg/mL, respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy human fetal lung fibroblast cells with an IC50 value of 118.34 µg/mL compared with that of cisplatin (IC50 = 10.08 µg/mL). TB-EO, its main component geraniol, TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed pronounced inhibitory properties against the replication of HSV-2 with the half-maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 µg/mL, respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26 and 108.25, respectively. TB-EO and geraniol at a concentration of 15 µg/mL showed prominent inhibitory activities against ACE with % of inhibition 95.4% and 92.2%, respectively, compared with that of standard inhibitor captopril (99.8%; 15 µg/mL). Molecular docking studies were performed to unveil the mechanism of action of geraniol as well as structural parameters necessary for anti-HSV-2 activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is the first report on the chemical composition of Egyptian TB-EO along with the above-mentioned biological activities. Our results may be considered as novel findings in the course of a search for new and active anticancer, anti-HSV-2 and antihypertensive agents, and expand the medicinal value of this plant and its phytochemicals in clinical practice.

scholarly journals In vitro Antidiabetic, anti-obesity and antioxidant proprities of Rosemary extracts

2014 ◽  
Vol 10 (2) ◽  
pp. 2305-2316 ◽  
Author(s):  
Manel Ben Ali ◽  
Kais Mnafgui ◽  
Abdelfattah Feki ◽  
Mohamed Damak ◽  
Noureddine Allouche
Keyword(s):  
Essential Oil ◽  
Ethyl Acetate ◽  
Pancreatic Lipase ◽  
Antioxidant Properties ◽  
Methanolic Extracts ◽  
Ic50 Values ◽  
Inhibitory Potential ◽  
Prevention Of Diabetes ◽  
First Time

Diabetes mellitus is a serious health problem worldwide that has adverse and long-lasting consequences for individuals, families, and communities. Hence, this study sought to investigate the inhibitory potential of rosemary extracts on key-enzymes related to diabetes such as α-amylase and pancreatic lipase activities, as well as to assess their antioxidant properties in vitro. The IC50 values of Rosemary essential oil, ethyl acetate and methanolic extracts against α-amylase were 28.36, 34.11 and 30.39 µg/mL respectively, and those against pancreatic lipase were 32.25, 36.64 and 34.07 µg/mL, suggesting strong anti-diabetic and anti-obesity effects of Rosemary. The methanolic extract was found to be the highest in levels of phenolic (282.98 µgGAE/mg extract) and flavonoids (161.05 µg QE /mg extract) contents as well as in the antioxidant activity (IC50 = 15.82 µg/mL) as compared to other extracts ethyl acetate (IC50 = 32.23 µg/mL) and essential oil  (IC50 = 96.12 µg/mL).Antioxidant efficacy of Rosemary extracts has been estimated in the stabilization of sunflower oil (SFO) at three different concentrations, i.e. 200 (SFO-200), 500 (SFO-500) and 1000 ppm (SFO-1000). Results showed the highest efficiency of SFO-1000.The results obtained in this study demonstrated for the first time that Rosemary is a potent source of natural inhibitors of α-amylase and pancreatic lipase with powerful antioxidants proprieties that might be used in the food stabilization and the prevention of diabetes and obesity complications as a complementary pharmacological drug.

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 Exploring Diverse-Ring Analogues on Combretastatin A4 (CA-4) Olefin as Microtubule-Targeting Agents

2020 ◽  
Vol 21 (5) ◽  
pp. 1817 ◽  
Author(s):  
Ming-Yu Song ◽  
Qiu-Rui He ◽  
Yi-Lin Wang ◽  
Hao-Ran Wang ◽  
Tian-Cheng Jiang ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Annexin V ◽  
Docking Studies ◽  
Cytotoxic Agents ◽  
Tubulin Polymerization ◽  
Microtubule Network ◽  
Microtubule Targeting Agents ◽  
Ic50 Values ◽  
Tubulin Polymerization Inhibitor

Combretastatin-4 (CA-4) as a tubulin polymerization inhibitor draws extensive attentions. However, due to its weak stability of cis-olefin and poor metabolic stability, structure modifications on cis-configuration are being performed. In this work, we constructed a series of novel CA-4 analogues with linkers on olefin containing diphenylethanone, cis-locked dihydrofuran, α-substituted diphenylethanone, cyclobutane and cyclohexane on its cis-olefin. Cytotoxic activity of all analogues was measured by an SRB assay. Among them, compound 6b, a by-product in the preparation of diphenylethanone analogues, was found to be the most potent cytotoxic agents against HepG2 cells with IC50 values of less than 0.5 μM. The two isomers of 6b induced cellular apoptosis tested by Annexin V-FITC and propidium iodide (PI) double staining, arrested cells in the G2/M phase by PI staining analysis, and disrupted microtubule network by immunohistochemistry study in HepG2 cells. Moreover, 6b-(E) displayed a dose-dependent inhibition effect for tubulin assembly in in vitro tubulin polymerization assay. In addition, molecular docking studies showed that two isomers of 6b could bind efficiently at colchicine binding site of tubulin similar to CA-4.

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