scholarly journals Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

2021 ◽  
Author(s):  
Govinda Rao Dabburu ◽  
Manish Kumar ◽  
Naidu Subbarao
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Simulation Studies ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Potential Inhibitors ◽  
Key Words Malaria ◽  
Leucyl Aminopeptidase

Abstract: Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP. Key words: Malaria, M17 Leucyl Aminopeptidase, ADMET, X-SCORE

scholarly journals MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

2020 ◽  
pp. 174-178
Author(s):  
SHAILENDRA SANJAY SURYAWANSHI ◽  
POOJA BHAVAKANA JAYANNACHE ◽  
RAJKUMAR SANJAY PATIL ◽  
PALLED MS ◽  
ALEGAON SG
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Studies ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors ◽  
Binding Energy Calculations ◽  
Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

scholarly journals Molecular docking studies of inhibitory activities of Phytochemicals in Calotropis procera against α-glucosidase hydrolase Sus B.

2021 ◽  
Vol 46 (2) ◽  
Author(s):  
O. O. Adeboye ◽  
S. A. Agboluaje ◽  
O. F. Akinyele
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Screening Tools ◽  
Inhibition Constant ◽  
Calotropis Procera ◽  
Docking Analysis ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Synthetic Drugs ◽  
Inhibitory Activities

The use of synthetic drugs is associated with various side effects and it is important to look for other drugs from medicinal plants. Therefore, this study aimed at assessing the inhibitory activities of Calotropis procera leaf against α-glucosidase hydrolase Sus B and it‟s possible mode of inhibiting this enzyme through molecular docking studies. From the molecular docking analysis, the results shows that out of the thirty six (36) screened phytochemicals, only twenty six (26) fall between the recommended hit value of inhibition constant of (0.1-1.0 µM) where their inhibition constant range from (0.01-0.59 µM) after docking with target receptor α-glucosidase hydrolase SusB (PDB ID: 2ZQ0) using Pyrx-vitual screening tools (Autodock tool, Autodock vina and Open babel).Visualizing was done using Pymol and Biosvia discovery studio(2019). Considering the other analysis done, Drug likeness of Lipinski rule of five, only six(6): Hesperidine (3),Calotroposide (3),Calotropin (3),Ascleposide (4),Proceroside (4) and Voruschairin (3) out of the potent twenty six (26) contravene more than 2 of the Lipinski rules of five, therefore other twenty (20) compounds can be considered for processing into potent drugs.

scholarly journals Mechanism of Cordyceps Cicadae in Treating Diabetic Nephropathy Based on Network Pharmacology and Molecular Docking Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yi Qian ◽  
Xin Sun ◽  
Xin Wang ◽  
Xin Yang ◽  
Mengyao Fan ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Docking ◽  
Docking Studies ◽  
New Drugs ◽  
Network Pharmacology ◽  
Active Components ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Cordyceps Cicadae ◽  
Molecular Docking Analysis

Objective. To systematically study the mechanism of cordyceps cicadae in the treatment of diabetic nephropathy (DN) with the method of network pharmacology and molecular docking analysis, so as to provide theoretical basis for the development of new drugs for the treatment of DN. Methods. TCMSP, Symmap, PubChem, PubMed, and CTD database were used to predict and screen the active components and therapeutic targets for DN. The network of active components and targets was drawn by Cytoscape 3.6.0, the protein-protein interaction (PPI) was analyzed by the STRING database, and the DAVID database was used for the enrichment analysis of intersection targets. Molecular docking studies were finished by Discovery Studio 3.5. Results. A total of 36 active compounds, including myriocin, guanosine, and inosine, and 378 potential targets of cordyceps cicadae were obtained. PPI network analysis showed that AKT1, MAPK8, and TP53 and other targets were related to both cordyceps cicadae and DN. GO and KEGG pathway analysis showed that these targets were mostly involved in R-HSA-450341, 157.14-3-3 cell cycle, and PDGF pathways. Docking studies suggested that myriocin can fit in the binding pocket of two target proteins (AKT1 and MAPK8). Conclusion. Active ingredients of cordyceps cicadae such as myriocin may act on DN through different targets such as AKT1, MAPK8, and TP53 and other targets, which can help to develop innovative drugs for effective treatment of DN.

scholarly journals In vitro and molecular docking studies of an antiinflammatory scaffold with human peroxiredoxin 5 and tyrosine kinase receptor

2020 ◽  
Vol 16 (11) ◽  
pp. 929-936
Author(s):  
R Bharathi ◽  
◽  
Keyword(s):  
Molecular Docking ◽  
Tyrosine Kinase ◽  
Diclofenac Sodium ◽  
Docking Studies ◽  
Tyrosine Kinase Receptor ◽  
Docking Analysis ◽  
Elemental Analyses ◽  
Anti Inflammatory ◽  
Potential Inhibitors

A new series of 4-(3-(2-amino-3,5-dibromophenyl)-1-(4-substitutedbenzoyl)-4,5-dihydro-1H-pyrazol-5-yl)benzonitrile (4a-h) compounds were synthesized and evaluated for in-vitro anti-inflammatory activities. The spectral (IR, NMR) and elemental analyses data of the product indicated the formation of new pyrazoles 4a-h. Compound 4e exhibited potent anti-inflammatory property with 85.45 % inhibitions. This value was compared with standard diclofenac sodium. This data is explained using molecular docking analysis of receptor-ligand binding. These results demonstrated that pyrazole derivatives are potential inhibitors of Human Peroxiredoxin 5 and Tyrosine kinase receptor in the treatment of inflammation related illness.

scholarly journals Molecular Docking Studies of SARS-Cov-2 Mainprotease Potential Inhibitors

2020 ◽  
Author(s):  
Wiji Utami ◽  
Ika Nur Fitriani ◽  
H A Aziz ◽  
Tanti Tanti ◽  
Pugoh Santoso
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Lipinski’S Rule ◽  
Discovery Studio ◽  
Inflammatory Agent ◽  
Docking Calculation ◽  
Fields Of Study ◽  
Calculation Results ◽  
Pass Online ◽  
Potential Inhibitors

Abstract BACKGROUND : SARS-Cov-2 causes an coronavirus disease 2019 (COVID-19), and the vaccines or drugs of this disease have not been found to inhibit this replication of the virus. Researchers are engaged in all fields of study to discover new potential inhibitors. This study aimed to compute the binding energy (BE) and interactions between the new potential inhibitors and the SARS-Cov-2 Mainprotease (Mpro).METHODS: In this study, we docked between twenty-seven patented drugs and the Mpro receptor (PDB ID: 6W63). The molecular docking calculation was performed using AutoDock Tools 1.5.6. software. Moreover, the information about the biological activity of ligands was calculated using the PASS online server. The result of the calculation was then analyzed and visualized using Biovia Discovery Studio Visualizer. Further calculation, such as the ligand-protein interaction using STITCH database and Lipinski’s rule five were employed in this research.RESULTS: The molecular docking calculation results showed that nelfinavir was strongly bound to Mpro with BE of -9,51 kcal/mol, followed by lopinavir, vitamin D, ritonavir, and dexamethasone. From these ligands, we considered dexamethasone because this ligand works as an anti-inflammatory agent. CONCLUSIONS: Following the calculation, nelfinavir, lopinavir, and dexamethasone are proposed as a potential inhibitor of the Mpro receptor, but there is a need for further investigation.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Joshua Oluwasegun Bamidele ◽  
George Oche Ambrose ◽  
Oluwaseun Suleiman Alakanse
Keyword(s):  
Molecular Docking ◽  
Liver Toxicity ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Computational Docking ◽  
Drug Candidates ◽  
Expression Rate ◽  
Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

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