scholarly journals Anti-Trypanosomal Potential of The Red Sea Soft Coral Nephthea Mollis Supported by Metabolomic Profiling and Molecular Docking Studies

2021 ◽  
Author(s):  
Khaled M. Allam ◽  
Yaser A. Mostafa ◽  
Usama R. Abdelmohsen ◽  
Amgad I.M. Khedr ◽  
Ahmed E. Allam ◽  
...  
Keyword(s):  
Ornithine Decarboxylase ◽  
Soft Coral ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Docking Study ◽  
Docking Studies ◽  
Metabolomic Profiling ◽  
In Silico Modeling ◽  
Lead Source

Abstract The total ethanol extract and its derived ethyl acetate fraction of the soft coral Nephthea mollis displayed remarkable in-vitro anti-trypanosomal potential against Trypanosoma brucei with IC50 value of 6.4 and 3.7 (µg/ml, 72 h respectively. Consequently, the total ethanol extract was subjected to LC-HR-ESI-MS metabolomic profiling to discover the constituents that possibly underlie their bioactivities. Therefore, thirty-three secondary metabolites were characterized, among them, sesquiterpenes and diterpenes were found to prevail. In silico modeling was carried out on the dereplicated compounds to provide an insight into their anti-trypanosomal mechanism of action with docking study on ornithine decarboxylase (ORD) which illustrated that five of the dereplicated compounds (‎2-deoxy-12-ethoxy-7-O-methyl lemnacarnol, Nephthenol, ‎4α-O-acetyl-selin-11-en, Eudesma-4,7(11)-diene-8β-ol, and Chabrolidione A) have the highest affinity to the ornithine decarboxylase enzyme. These results highlight the valuable chemical profile of Nephthea mollis as a lead source for anti-trypanosomal natural products.

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 Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

2020 ◽  
Vol 32 (6) ◽  
pp. 1482-1490
Author(s):  
Manju Mathew ◽  
Raja Chinnamanayakar ◽  
Ezhilarasi Muthuvel Ramanathan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Adme Prediction ◽  
Antimicrobial Studies ◽  
In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

scholarly journals Monoamine Oxidase Inhibitory Activity of Biflavonoids from Branches of Garcinia gardneriana (Clusiaceae)

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Maria Angélica Recalde-Gil ◽  
Luiz Carlos Klein-Júnior ◽  
Carolina dos Santos Passos ◽  
Juliana Salton ◽  
Sérgio Augusto de Loreto Bordignon ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Spectrometric Data ◽  
Mao B ◽  
Inhibitory Compounds ◽  
Mao A ◽  
Mao Activity

Garcinia gardneriana is chemically characterized by the presence of biflavonoids. Taking into account that flavonoids are able to inhibit monoamine oxidase (MAO) activity, in the present study, the chemical composition of the branches’ extract of the plant is described for the first time and the MAO inhibitory activity of the isolated biflavonoids was evaluated. Based on spectroscopic and spectrometric data, it was possible to identify volkesiflavone, morelloflavone (1), Gb-2a (2) and Gb-2a-7- O-glucoside (3) in the ethyl acetate fraction from ethanol extract of the branches. Compounds 1-3 were evaluated in vitro and demonstrated the capacity to inhibit MAO-A activity with an IC50 ranging from 5.05 to 10.7 μM, and from 20.7 to 66.2 μM for MAO-B. These inhibitions corroborate with previous IC50 obtained for monomeric flavonoids, with a higher selectivity for MAO-A isoform. The obtained results indicate that biflavonoids might be promising structures for the identification of new MAO inhibitory compounds.

Pyrazole Schiff Base Hybrids as Anti-Malarial Agents: Synthesis, In Vitro Screening and Computational Study

2018 ◽  
Vol 21 (3) ◽  
pp. 194-203 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Schiff Base ◽  
Antimalarial Activity ◽  
Computational Study ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Study Results ◽  
Wide Range ◽  
Parasite Plasmodium Falciparum

Background: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy. Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain. Materials & Methods: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction. Results: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies. Conclusion: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.

scholarly journals Antidiabetic Activity ofPterospermum acerifoliumFlowers and Glucose Uptake Potential of Bioactive Fraction in L6 Muscle Cell Lines with Its HPLC Fingerprint

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Rathinavelusamy Paramaguru ◽  
Papiya Mitra Mazumder ◽  
Dinakar Sasmal ◽  
Venkatesan Jayaprakash
Keyword(s):  
Glucose Uptake ◽  
Fasting Blood Glucose ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Diabetic Control ◽  
Antidiabetic Activity ◽  
Peripheral Tissues ◽  
Hplc Fingerprint

The present study was designed to estimate the detailed antidiabetic activity ofPterospermum acerifolium(L.) Willd flowers.In vitroalpha amylase inhibition study was carried out on 50% ethanol extract of flowers (PAFEE) and its various fractions. The active ethyl acetate fraction (PAFEF) was subfractionated into three subfractions (PAFE1, PAFE2, and PAFE3) and subjected to acute toxicity studies followed by antidiabetic screeningin vivoby streptozotocin-nicotinamide induced type II diabetes. Diabetic animals treated with PAFE2 (30 mg/kg) reduced the levels of fasting blood glucose, significantly (P<0.001) compared to that of diabetic control animals. Histological studies on drug treated groups did not show remarkable positive changes inβ-cells. PAFE2 showed32.6±1.93% glucose uptake over control and, in the presence of PI3K inhibitor wortmannin, declined to13.7±2.51%. HPLC analysis of PAFE2 reveals the presence of quercetin and apigenin as major constituents and both are inhibiting the glycogen phosphorylase enzyme in molecular modelling studies. The study evidenced strongly that the probable glucose lowering mechanism of action of active subfraction PAFE2 is by increasing the glucose uptake in peripheral tissues and by inhibition of gluconeogenesis.

scholarly journals Neuroprotective Effect of Metaplexis japonica against in vitro Ischemia Model

2019 ◽  
Vol 3 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Nirmala Jamarkattel-Pandit ◽  
Hocheol Kim
Keyword(s):  
Cell Damage ◽  
Neuroprotective Effect ◽  
Ethanol Extract ◽  
Glucose Deprivation ◽  
Ethyl Acetate Fraction ◽  
Perennial Herb ◽  
Oxygen Glucose Deprivation ◽  
In Vitro Ischemia ◽  
Ht22 Cell

Metaplexis japonica (Apocynaceae) is a perennial herb, extensively used in traditional medicinal system for various diseases. The purpose of the study was to evaluate the protective effect of M. japonica against in vitro ischemia. In the present study, 70% ethanol extract of M. japonica was fractionated with different polarity solvents. For in vitro ischemia, oxygen-glucose deprivation followed by reoxygenation (OGD-R) in cells was used to investigate the effects of M. japonica and its fractions. For oxidative stress model, Hydrogen peroxide (H2 O2 ) induced cell death was studied in HT22 cell line. M. japonica and its fractions significantly reduced the HT22 cell damage, which was induced by 4 hrs of OGD followed by 24 hrs of reoxygenation and 24 hrs of H2 O2, respectively. The effectiveness of ethyl acetate fraction was higher than other fractions/crude extract. Our results suggest that M. japonica could be a neuroprotective agent for the treatment of stroke. Key words: Metaplexis japonica, Stroke, Oxygen-glucose deprivation, Neuroprotection

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

scholarly journals Screening Bioactivity of Kersen Fruits (Muntingia calabura L.) as a Sunscreens Candidate

2021 ◽  
Vol 7 (1) ◽  
pp. 29-38
Author(s):  
Syamsu Nur ◽  
Nursamsiar Nursamsiar ◽  
Muhammad Aswad ◽  
Aprilia Ester Eunike Tumigolung ◽  
Risfah Yulianti ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Active Ingredient ◽  
Ethanol Extract ◽  
Ethyl Acetate Fraction ◽  
Flavonoid Content ◽  
In Vitro Method ◽  
Best Value ◽  
Phenolic And Flavonoid ◽  
Muntingia Calabura

Kersen (Muntingia calabura L) fruits have the potential to be used as an active ingredient in sunscreens because of phenolic and flavonoid content that can absorb UV rays. This study aims to determine the percentage of erythema/pigmentation transmission and SPF value as parameters for sunscreen activity.  Kersen fruits were extracted by maceration using 96% ethanol. The ethanol extract of Kersen Fruits was also fractionated to separate the components of the active compounds based on the polarity level using n-hexane, ethyl acetate, and ethanol as solvents. The test was carried out using the in vitro method by measuring the ability of the material to absorb ultraviolet light at a wavelength of 292.5-372.5 nm. This research was conducted at concentrations of 100, 200, 400, 600, and  800 µg/mL for ethanol, lyophilisate, n-hexane, and ethanol fractions, while the ethyl acetate fraction concentrations are 50, 100, 150, 200, 250 µg/mL. The results showed the best value at the ethyl acetate fraction concentration of 250 µg/mL with % Te of 5.28 and % Tp of 28.65 and the SPF value of 16.54. Based on the % Te and Tp, the ethyl acetate fraction exhibited protection against erythema and pigmentation with the category of extra protection and based on the SPF value with the category of ultra protection.

scholarly journals MOLECULAR DOCKING STUDY ON 1H-(3,4d) PYRAZOLO-PYRIMIDINES AS CYCLIN DEPENDANT KINASE (CDK2) INHIBITORS

2016 ◽  
Vol 9 (1) ◽  
pp. 94
Author(s):  
Manisha S. Phoujdar ◽  
Gourishankar R. Aland
Keyword(s):  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Van Der Waals Interactions ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Receptor Assays

Objective: CDK2 inhibitors are implicated in several carcinomas viz. Carcinoma of lung, bladder, sarcomas and retinoblastoma. Pyrazolopyrimidines, being purine bioisosters inhibit more than one type of kinase. In this study, we are studying some novel derivatives of 1H-pyrazolo [3,4d] pyrimidines not reported earlier. The objective of the present study is an attempt towards design and development of 1H-[3,4-] pyrazolo-pyrimidines as CDK2 inhibitors through rational drug design.Methods: The present study has been done on CDK2 structure, PDB ID, 3WBL, co-crystallized with ligand PDY from RCSB protein data bank. A series of seventeen 1H-Pyrazolo [3,4-d] pyrimidines feasible for synthesis was docked on the said CDK2 receptor using Auto Dock 4 version, 1.5.6. Outputs were exported to discovery studio 3.5 client for visual inspection of the binding modes and interactions of the compounds with amino acid residues in the active sites.Results: The results of docking studies revealed that the present series of 1H-Pyrazolo[3,4-d] pyrimidines is showing significant binding through hydrogen bonding, hydrophobic, pi and Van der waals interactions, similar to the ligand PDY. Some conserved H-bond interactions comparable to bioisosters and compounds presently under human trials were noted. Ki values predicted in silico also suggest that the series will show promising CDK2 inhibitory activity.Conclusion: The series designed and docked can be further developed by synthesis and in vitro and in vivo activity. The receptor inhibitory activity can also be checked by specific receptor assays.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

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