In Vitro Antioxidant, Antimicrobial and Molecular Docking Studies of Fosphenytoin and Regadenoson Impurities

2020 ◽  
Vol 8 (1) ◽  
pp. 63-69
Author(s):  
S. Sathiyanarayanan ◽  
◽  
C.S. Venkatesan ◽  
S. Kabilan ◽  
◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Product ◽  
Active Pharmaceutical Ingredient ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Gaba A ◽  
Pharmacokinetic Properties ◽  
Approved Drugs

Regadenoson and Fosphenytoin are USFDA approved drugs which is used for coronary vasodilator and convulsive status epileptics respectively. It is quite natural that low levels of reagents or side products are present in the final active pharmaceutical ingredient (API) or drug product as impurities. Such impurities may have unwanted toxicities, including genotoxicity and carcinogenicity. Hence, it is important to study on impurities present in both the drugs. There are 9 impurities were identified from both drugs and studied pharmacokinetic properties using Qikprop module from Schrödinger software. From the 9 compounds of both the drug’s impurities, 5 compounds obey the Lipinski rule of five and the remaining compounds are having 1 to 3 penalties. All the compounds were subjected to molecular docking study with thermo stabilised HUMAN A2A Receptor with adenosine bound protein (PDB ID: 2YDO) for regadenoson impurities and fosphenytoin impurities were docked with Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation A protein (PDB id: 6D6U). All the compounds are showed very good interaction with docked proteins. Further selected compound subjected to in vitro Antibacterial (Gram positive, Gram negative), Antifungal and Antioxidant (DPPH and FRAP) studies.

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

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.

Design, Synthesis, Molecular Docking Study and Anti-Hepatocellular Carcinoma Evaluation of New Bis-Triazolothiadiazines

2020 ◽  
Vol 20 (9) ◽  
pp. 788-800 ◽  
Author(s):  
Sobhi M. Gomha ◽  
Zeinab A. Muhammad ◽  
Elham Ezz El-Arab ◽  
Amira M. Elmetwally ◽  
Abdelaziz A. El-Sayed ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Modes ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Reference Drug ◽  
Ic50 Value

Objective: The reaction of bis(4-amino-4H-1,2,4-triazole-3-thiol) with hydrazonoyl halides and α-halo-ketones gave a new series of bis-1,2,4-triazolo[3,4-b]thiadiazine derivatives. Methods: The structure of the new products was established on the basis of their elemental and spectral data (mass, 1H NMR, 13C NMR and IR) and an alternate method. Results: Several of the synthesized products were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HepG-2) and the results showed that compounds 16, 14 and 12 have promising activities (IC50 value of 24.8±9.1, 28.3±0.5, and 31±2.9μM, respectively) compared with Harmine reference drug (IC50 value of 22.4±1.11 μM). Conclusion: Moreover, molecular docking studies were performed to analyze the binding modes of the discovered hits into the active site of DYRK1A using iGEMDOCK.

Pyridine and Benzoisothiazole Decorated Vanillin Chalcones: Synthesis, Antimicrobial, Antioxidant, Molecular Docking Study and ADMET Properties

2020 ◽  
Vol 17 (5) ◽  
pp. 367-381
Author(s):  
Pintu Pathare ◽  
Sunil Tekale ◽  
Rafique Shaikh ◽  
Manoj Damale ◽  
Jaiprakash Sangshetti ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Docking Study ◽  
Docking Studies ◽  
Pharmacokinetic Parameters ◽  
Molecular Docking Study ◽  
Antimicrobial Drugs ◽  
Discovery Studio ◽  
Pharmacokinetic Properties

Background: The search for new antimicrobial drugs is a never ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to human kind. Objective: The present studies were aimed to synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones. Materials and Methods: FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against diffenet bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict toxicity profile of the compounds using FAFDrugs2 predictor. Results: The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives. Conclusion: Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process.

scholarly journals A Comparative Study of Approved Drugs for SARS-CoV-2 by Molecular Docking

2021 ◽  
Vol 1 (1) ◽  
pp. 25-31
Author(s):  
Achal Mishra ◽  
Radhika Waghela
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Target Protein ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Drug Molecules ◽  
Main Protease ◽  
New Type ◽  
Approved Drugs

SARS-CoV-2, a new type of Coronavirus, has affected more millions of people worldwide. From the spread of this infection, many studies related to this virus and drug designing for the treatment have been started. Most of the studies target the SARS-CoV-2 main protease, spike protein of SASR-CoV-2, and some are targeting the human furin protease. In the current work, we chose the clinically used drug molecules remdesivir, favipiravir, lopinavir, hydroxychloroquine, and chloroquine onto the target protein SARS-CoV-2 main protease. Docking studies were performed using Arguslab, while Discovery Studio collected 2D and 3D pose views with the crystal structure of COVID-19 main protease in complex with an inhibitor N3 with PDB ID 6LU7. Computational studies reveal that all ligands provided good binding affinities towards the target protein. Among all the chosen drugs, lopinavir showed the highest docking score of -11.75 kcal/mol. The results from this molecular docking study encourage the use of lopinavir as the first-line treatment drug due to its highest binding affinity.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

An insight on safety, efficacy, and molecular docking study reports of N-acetylcysteine and its compound formulations

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Laiba Rind ◽  
Mohammad Ahmad ◽  
Mohammad Irfan Khan ◽  
Badruddeen ◽  
Juber Akhtar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Analytical Techniques ◽  
Docking Study ◽  
Biological Properties ◽  
Docking Studies ◽  
Pharmaceutical Product ◽  
Fixed Dose ◽  
Molecular Docking Study

Abstract N-acetylcysteine (NAC) is considered as the body’s major antioxidant molecules with diverse biological properties. In this review, the pharmacokinetics, safety and efficacy report on both the preclinical and clinical summary of NAC is discussed. Both in vitro and in vivo preclinical studies along with the clinical data have shown that NAC has enormous biological properties. NAC is used in the treatment of acetaminophen poisoning, diabetic nephropathy, Alzheimer’s disease, schizophrenia, and ulcerative colitis, etc. Numerous analytical techniques, for instance, UPLC, LC-MS, HPLC, RP-IPC are primarily employed for the estimation of NAC in different single and fixed-dose combinations. The molecular docking studies on NAC demonstrate the binding within Sudlow’s site-I hydrogen bonds and formation of NAC and BSA complexes. Various hydrophobic and hydrophilic amino acids generally exist in making contact with NAC as NAC-BSA complexes. Docking studies of NAC with the active site of the urease exposed an O-coordinated bond through nickel 3002 and a hydrogen bond through His-138. NAC and its analogs also made the allosteric pockets that helped to describe almost all favorable pose for the chaperone in a complex through the protein. Thus, we intended to highlight the several health benefits of this antioxidant compound and applications in pharmaceutical product development.

scholarly journals Biological Evaluation and Molecular Docking Studies of Benzalkonium Ibuprofenate

2020 ◽  
Author(s):  
Kodakkat Parambil Safna Hussan ◽  
Mohamed Shahin Thayyil ◽  
Thaikadan Shameera Ahamed ◽  
Karuvanthodi Muraleedharan
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Performance Enhancement ◽  
Docking Study ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Anti Inflammatory ◽  
Delivery Options

The third-generation ionic liquids (ILs), which are being used to produce double active pharmaceutical ingredients (d-APIs) with tunable biological activity along with novel performance, enhancement, and delivery options, have been revolutionizing the area of drug discovery since the past few decades. Herein we report the in vitro antibacterial and anti-inflammatory activity of benzalkonium ibuprofenate (BaIb) that are being used as in-house d-API, with a particular focus on its interaction with respective protein target through molecular docking study. The evaluation of the biological activity of BaIb with the antibacterial and anti-inflammatory target at the molecular level revealed that the synthesized BaIb could be designed as a potential double active drug since it retains the antibacterial and anti-inflammatory activity of its parent drugs, benzalkonium chloride (BaCl) and sodium ibuprofenate (NaIb), respectively.

scholarly journals In silico Assessment and Molecular Docking Studies of Some Phyto-Triterpenoid for Potential Disruption of Mortalin-p53 Interaction

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1983
Author(s):  
Minh Quan Pham ◽  
Thuy Huong Le Thi ◽  
Quoc Long Pham ◽  
Le Thi Le ◽  
Huy Toan Dao ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Transcriptional Activation ◽  
Docking Study ◽  
Docking Studies ◽  
Common Type ◽  
Inhibition Activity ◽  
Molecular Docking Study ◽  
Chemotherapy Drugs ◽  
Anti Cancer ◽  
Pharmacokinetic Properties

Human hepatocellular carcinoma (HCC), the most common type of liver cancer, represents the second most common cause of death from cancer worldwide. The high toxicity and side effects of some cancer chemotherapy drugs increase the demand for new anti-cancer drugs from natural products. Mortalin/mtHsp70, a stress response protein, has been reported to contribute to the process of carcinogenesis in several ways, including the inhibition of the transcriptional activation of p53. This study conducted a molecular docking study of 41 phyto triterpenes originated from Vietnamese plants for potential Mortalin inhibition activity. Nine compounds were considered as promising inhibitors based on the analysis of binding affinity and drug-like and pharmacokinetic properties.

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