Structure-activity and anti-platelet aggregation mechanism of a non-toxic 5′-nucleotidase: Molecular docking and binding interaction study

2017 ◽  
Vol 280 ◽  
pp. S200 ◽  
Author(s):  
Samah Saoud ◽  
Fatah Cherifi ◽  
Safia Kellou-Tairi ◽  
Fatima Laraba-Djebari
Keyword(s):  
Molecular Docking ◽  
Platelet Aggregation ◽  
Interaction Study ◽  
Binding Interaction ◽  
Aggregation Mechanism ◽  
Structure Activity

scholarly journals IN SILICO BINDING INTERACTION STUDY OF MEFENAMIC ACID AND PIROXICAM ON HUMAN ALBUMIN

2017 ◽  
Vol 9 ◽  
pp. 102
Author(s):  
Joshita Djajadisastra ◽  
Hamka Decky Purnama ◽  
Arry Yanuar
Keyword(s):  
Molecular Docking ◽  
Mefenamic Acid ◽  
Free Fraction ◽  
Human Albumin ◽  
Binding Energies ◽  
Interaction Study ◽  
Binding Interaction ◽  
Knowing That ◽  
Pharmacological Response ◽  
Binding Position

Objective: A drug can replace other drugs in the same binding position in protein plasma, increasing pharmacological response due to the increasedfree drug concentration. Drug shifting is critical when a compound is tightly bound to a protein. For example, a binding fraction change, from 98% to94%, may increase the free fraction 3 times, from 2% to 6%. Knowing that there is an interaction between mefenamic acid and piroxicam on plasmaprotein, more specifically on human albumin, this study aimed to visualize the interaction between both drugs and human albumin in silico.Methods: This study used AutoDock4 as a molecular docking technique, obtaining binding visualizations, binding energies (ΔG), and inhibitionconstants (Ki) of both mefenamic acid-albumin and piroxicam-albumin bindings.Results: It is shown that the ΔG and Ki of both mefenamic acid and piroxicam are −5.47 kcal/mol (98.59 μM) and −7.46 kcal/mol (3.42 μM), respectively.Conclusions: The process of binding mefenamic acid to albumin can be substituted with piroxicam due to its higher ΔG and Ki values. It can bepredicted that this interaction will increase the free mefenamic acid concentration in blood plasma which, in turn, enhances the therapeutic effect.

scholarly journals Thiazole Based Carbohydrazide Derivatives as α-Amylase Inhibitor and Their Molecular Docking Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Muhammad Taha ◽  
Maryam Irshad ◽  
Syahrul Imran ◽  
Fazal Rahim ◽  
Manikandan Selvaraj ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Docking Studies ◽  
Antidiabetic Agent ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Structure Activity ◽  
Inhibitory Potential ◽  
Amylase Inhibitors

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

scholarly journals Study of Components and Mechanism of Juechuang Against Platelet Aggregation Based on Network Pharmacology

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2094129
Author(s):  
Zhou-Tao Xie ◽  
Bo Liu ◽  
Yi-yi Xiong ◽  
Yan-Fang Yang ◽  
He-Zhen Wu
Keyword(s):  
Molecular Docking ◽  
Platelet Aggregation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Active Ingredients ◽  
Aggregation Mechanism ◽  
Antiplatelet Aggregation

Juechuang, a traditional Chinese herbal medicine, is originated from Rostellularia procumbens (L.) Nees. Many studies have shown that the ethyl acetate extract from Juechaung may inhibit platelet aggregation. However, the antiplatelet aggregation mechanism of Juechuang requires more systematic research. In this article, network pharmacology was used to explore the antiplatelet aggregation components and its antiplatelet aggregation mechanism. Different components were evaluated and screened by pharmacokinetic characteristics. The potential targets of active ingredients were predicted by a reverse pharmacophore matching method, and the targets were screened according to targets related to antiplatelet aggregation in the GeneCards database. Thus, an interaction network of component-target-pathway of Juechuang was generated using Cytoscape 3.2.1. software. Furthermore, the binding energy of relevant active components with key targets was calculated using a Lamarck genetic algorithm in the molecular docking calculations. Finally, the study identified 28 potentially active ingredients in Juechuang, providing further evidence that the active ingredients act on 277 targets, and 38 protein targets related to antiplatelet aggregation were screened. Through the Kyoto encyclopedia of genes and genome pathway enrichment analysis, we found that the mechanism of antiplatelet aggregation may be related to the Ras signaling pathway, platelet activation signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. Via molecular docking of 2 targets, non-receptor tyrosine kinases(SRC) and MAPK were selected for molecular docking. By comparing the molecular docking results of Chinensinaphthol, Taiwanin E, Tuberculatin, Cycloeucalenol, and Justicidin B to the control drug, we found that those test molecules combined with targets and lead to high binding activity. These molecular docking results were also consistent with the literature values, and they helped identify the active ingredients and assured the reliability of the network analysis. This study may further provide a reference for the systematic study of the pharmacodynamic effect and the antiplatelet aggregation mechanism of Juechuang.

scholarly journals Synthesis of Chromen-4-One-Oxadiazole Substituted Analogs as Potent β-Glucuronidase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1528 ◽  
Author(s):  
Muhammad Taha ◽  
Fazal Rahim ◽  
Muhammad Ali ◽  
Muhammad Naseem Khan ◽  
Mohammed A. Alqahtani ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Inhibitory Activity ◽  
Docking Studies ◽  
Activity Relationship ◽  
Variable Degree ◽  
Binding Interaction ◽  
Molecular Docking Studies ◽  
Structure Activity ◽  
Ic50 Values

Chromen-4-one substituted oxadiazole analogs 1–19 have been synthesized, characterized and evaluated for β-glucuronidase inhibition. All analogs exhibited a variable degree of β-glucuronidase inhibitory activity with IC50 values ranging in between 0.8 ± 0.1–42.3 ± 0.8 μM when compared with the standard d-saccharic acid 1,4 lactone (IC50 = 48.1 ± 1.2 μM). Structure activity relationship has been established for all compounds. Molecular docking studies were performed to predict the binding interaction of the compounds with the active site of enzyme.

Synthesis, In-vitro and Docking Analysis of C-3 substituted Coumarin Analogues as Anticancer Agents C-3 Substituted Coumarins as Anticancer Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Anuradha Thakur ◽  
Kamalpreet Kaur ◽  
Praveen Sharma ◽  
Ramit Singla ◽  
Sandeep Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Anticancer Agents ◽  
Proliferative Activity ◽  
Binding Interaction ◽  
Diverse Range ◽  
Mcf 7 ◽  
Substituted Coumarins

Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effect along with multi-drug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking. Method: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues 12 and 13 show good antiproliferative activity with IC50 values 1and 1.3 µM respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit dock score of -4.10 kcal/mol and -4.38 kcal/mol respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future.

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.

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

2020 ◽  
Vol 20 (14) ◽  
pp. 1714-1721
Author(s):  
Hatem A. Abuelizz ◽  
El Hassane Anouar ◽  
Mohamed Marzouk ◽  
Mizaton H. Hasan ◽  
Siti R. Saleh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kojic Acid ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Amino Acid Residues ◽  
New Class ◽  
Structure Activity ◽  
Tyrosinase Inhibitors ◽  
Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

scholarly journals Discovery of New Inhibitors of Transforming Growth Factor-Beta Type 1 Receptor by Utilizing Docking and Structure-Activity Relationship Analysis

2019 ◽  
Vol 20 (17) ◽  
pp. 4090 ◽  
Author(s):  
Jiang ◽  
Deng
Keyword(s):  
Molecular Docking ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Binding Modes ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Growth Factor Beta ◽  
New Compounds

The transforming growth factor-beta (TGF-β) plays an important role in pathological fibrosis and cancer transformation. Therefore, the inhibition of the TGF-β signaling pathway has therapeutic potential in the treatment of cancer. In this study, the binding modes between 47 molecules with a pyrrolotriazine-like backbone structure and transforming growth factor-beta type 1 receptor (TβR1) were simulated by molecular docking using Discovery Studio software, and their structure–activity relationships were analyzed. On the basis of the analysis of the binding modes of ligands in the active site and the structure–activity relationships, 29,254 new compounds were designed for virtual screening. According to the aforementioned analyses and Lipinski’s rule of five, five new compounds (CQMU1901–1905) with potential activity were screened through molecular docking. Among them, CQMU1905 is an attractive molecule composed of 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), and 5-azacytosine. Interestingly, 5-FU, 6-MP, and 5-azacytidine are often used as anti-metabolic agents in cancer treatment. Compared with existing compounds, CQMU1901–1905 can interact with target proteins more effectively and have good potential for modification, making them worthy of further study.

Sign in / Sign up

Export Citation Format

Share Document