scholarly journals Neuroprotective potentials of selected natural edible oils using enzyme inhibitory, kinetic and simulation approaches

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mater H. Mahnashi ◽  
Bandar A. Alyami ◽  
Yahya S. Alqahtani ◽  
Ali O. Alqarni ◽  
Muhammad Saeed Jan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Drug Targets ◽  
Edible Oils ◽  
Zingiber Officinale ◽  
Docking Studies ◽  
Gas Chromatography Mass Spectrometry ◽  
Amino Acid Residues ◽  
Anionic Site ◽  
Cinnamon Oil ◽  
Docking Simulations

Abstract Background Edible oils have proven health benefits in the prevention and treatment of various disorders since the establishment of human era. This study was aimed to appraise neuropharmacological studies on the commonly used edible oils including Cinnamomum verum (CV), Zingiber officinale (ZO) and Cuminum cyminum (CC). Methods The oils were analyzed via GC-MS for identifications of bioactive compounds. Anti-radicals capacity of the oils were evaluated via 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals scavenging assays. The samples were also tested against two important acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which are among the important drug targets in Alzheimer’s disease. Lineweaver-Burk plots were constructed for enzyme inhibition studies which correspond to velocity of enzymes (Vmax) against the reciprocal of substrate concentration (Km) in the presence of test samples and control drugs following Michaelis-Menten kinetics. Docking studies on AChE target were also carried out using Molecular Operating Environment (MOE 2016.0802) software. Results (Gas chromatography-mass spectrometry GC-MS) analysis revealed the presence of thirty-four compounds in Cinnamon oil (Cv.Eo), fourteen in ginger oil (Zo.Eo) and fifty-six in cumin oil (Cc.Eo). In the antioxidant assays, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC50 values of 85, 121, 280 μg/ml sequentially against DPPH radicals. Whereas, in ABTS assay, Cv.Eo, Zo.Eo and Cc.Eo showed considerable anti-radicals potentials with IC50 values of 93, 77 and 271 μg/ml respectively. Furthermore, Cv.Eo was highly active against AChE enzyme with IC50 of 21 μg/ml. Zo.Eo and Cc.Eo exhibited considerable inhibitory activities against AChE with IC50 values of 88 and 198 μg/ml respectively. In BChE assay, Cv.Eo, Zo.Eo and Cc.Eo exhibited IC50 values of 106, 101 and 37 μg/ml respectively. Our results revealed that these oils possess considerable antioxidant and cholinesterase inhibitory potentials. As functional foods these oils can be effective remedy for the prevention and management of neurological disorders including AD. Synergistic effect of all the identified compounds was determined via binding energy values computed through docking simulations. Binding orientations showed that all the compounds interact with amino acid residues present in the peripheral anionic site (PAS) and catalytic anionic site (CAS) amino acid residues, oxyanion hole and acyl pocket via π-π stacking interactions and hydrogen bond interactions.

scholarly journals Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Prasanna A. Datar ◽  
Sonali R. Jadhav
Keyword(s):  
Amino Acid ◽  
Docking Studies ◽  
Diabetic Rats ◽  
Hypoglycemic Activity ◽  
Amino Acid Residues ◽  
Docking Score ◽  
Design And Synthesis ◽  
Hypoglycaemic Agents ◽  
Standard Compound

Pyrazole-3-one compounds were designed on the basis of docking studies of previously reported antidiabetic pyrazole compounds. The amino acid residues found during docking studies were used as guidelines for the modification of aromatic substitutions on pyrazole-3-one structure. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to in vivo hypoglycemic activity using alloxan induced diabetic rats and metformin as a standard. Compound 4 having sulphonamide derivative was found to be the most potent compound among the series.

scholarly journals A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein

2020 ◽  
Vol 7 ◽  
Author(s):  
Rounak Chourasia ◽  
Srichandan Padhi ◽  
Loreni Chiring Phukon ◽  
Md Minhajul Abedin ◽  
Sudhir P. Singh ◽  
...  
Keyword(s):  
Drug Targets ◽  
Docking Studies ◽  
Lactobacillus Delbrueckii ◽  
Amino Acid Residues ◽  
Main Protease ◽  
Effective Inhibition ◽  
Cheese Peptides ◽  
Potential Inhibitors

The COVID-19 pandemic caused by novel SARS-CoV-2 has resulted in an unprecedented loss of lives and economy around the world. In this study, search for potential inhibitors against two of the best characterized SARS-CoV-2 drug targets: S1 glycoprotein receptor-binding domain (RBD) and main protease (3CLPro), was carried out using the soy cheese peptides. A total of 1,420 peptides identified from the cheese peptidome produced using Lactobacillus delbrueckii WS4 were screened for antiviral activity by employing the web tools, AVPpred, and meta-iAVP. Molecular docking studies of the selected peptides revealed one potential peptide “KFVPKQPNMIL” that demonstrated strong affinity toward significant amino acid residues responsible for the host cell entry (RBD) and multiplication (3CLpro) of SARS-CoV-2. The peptide was also assessed for its ability to interact with the critical residues of S1 RBD and 3CLpro of other β-coronaviruses. High binding affinity was observed toward critical amino acids of both the targeted proteins in SARS-CoV, MERS-CoV, and HCoV-HKU1. The binding energy of KFVPKQPNMIL against RBD and 3CLpro of the four viruses ranged from −8.45 to −26.8 kcal/mol and −15.22 to −22.85 kcal/mol, respectively. The findings conclude that cheese, produced by using Lb. delbrueckii WS4, could be explored as a prophylactic food for SARS-CoV-2 and related viruses. In addition, the multi-target inhibitor peptide, which effectively inhibited both the viral proteins, could further be used as a terminus a quo for the in vitro and in vivo function against SARS-CoV-2.

scholarly journals Molecular docking-based test for affinities of two ligands toward vasopressin and oxytocin receptors.

2001 ◽  
Vol 48 (1) ◽  
pp. 131-135 ◽  
Author(s):  
R Slusarz ◽  
R Kaźmierkiewicz ◽  
A Giełdoń ◽  
B Lammek ◽  
J Ciarkowski
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Ligand Binding ◽  
Effective Procedure ◽  
Amino Acid Residues ◽  
Receptor Ligand ◽  
Docking Simulations ◽  
Oxytocin Receptors ◽  
Developing Area

Molecular docking simulations are now fast developing area of research. In this work we describe an effective procedure of preparation of the receptor-ligand complexes. The amino-acid residues involved in ligand binding were identified and described.

scholarly journals An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA2fromCrotalus durissus terrificus

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Daniela de Oliveira Toyama ◽  
Henrique Hessel Gaeta ◽  
Marcus Vinícius Terashima de Pinho ◽  
Marcelo José Pena Ferreira ◽  
Paulete Romoff ◽  
...  
Keyword(s):  
Amino Acid ◽  
Docking Studies ◽  
Pharmacological Effects ◽  
Amino Acid Residues ◽  
Substrate Molecule ◽  
Pharmacological Activities ◽  
Potent Inhibition ◽  
Crotalus Durissus

This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA2) fromCrotalus durissus terrificus, which is the main toxin involved in the pharmacological effects of this snake venom. According to our mass spectrometry and circular dichroism results, quercetin was able to promote a chemical modification of some amino acid residues and modify the secondary structure ofC. d. terrificussPLA2. Moreover, molecular docking studies showed that quercitrin can establish chemical interactions with some of the crucial amino acid residues involved in the enzymatic activity of the sPLA2, indicating that this flavonoid could also physically impair substrate molecule access to the catalytic site of the toxin. Additionally,in vitroandin vivoassays showed that the quercitrin strongly diminished the catalytic activity of the protein, altered its Vmax and Km values, and presented a more potent inhibition of essential pharmacological activities in theC. d. terrificussPLA2, such as its myotoxicity and edematogenic effect, in comparison to quercetin. Thus, we concluded that the rhamnose group found in quercitrin is most likely essential to the antivenom activities of this flavonoid againstC. d. terrificussPLA2.

Molecular cloning and characterization of a M17 leucine aminopeptidase of Cryptosporidium parvum

Parasitology ◽  
2011 ◽  
Vol 138 (6) ◽  
pp. 682-690 ◽  
Author(s):  
J.-M. KANG ◽  
H.-L. JU ◽  
W.-M. SOHN ◽  
B.-K. NA
Keyword(s):  
Amino Acid ◽  
Cryptosporidium Parvum ◽  
Metal Binding ◽  
Drug Targets ◽  
Leucine Aminopeptidase ◽  
Biochemical Properties ◽  
Site Formation ◽  
Amino Acid Residues ◽  
Multiple Sequence ◽  
Binding Characteristics

SUMMARYLeucine aminopeptidases (LAPs) are a group of metalloexopeptidases that catalyse the sequential removal of amino acids from the N-termini of polypeptides or proteins. They play an important role in regulating the balance between catabolism and anabolism in living cells. LAPs of apicomplexa parasitic protozoa have been intensively investigated due to their crucial roles in parasite biology as well as their potentials as drug targets. In this study, we identified an M17 leucine aminopeptidase of Cryptosporidium parvum (CpLAP) and characterized the biochemical properties of the recombinant protein. Multiple sequence alignment of the deduced amino acid sequence of CpLAP with those of other organisms revealed that typical amino acid residues essential for metal binding and active-site formation in M17 LAPs were well conserved in CpLAP. Recombinant CpLAP shared similar biochemical properties such as optimal pH, stability at neutral pHs, and metal-binding characteristics with other characterized LAPs. The enzyme showed a marked preference for Leu and its activity was effectively inhibited by bestatin. These results collectively suggest that CpLAP is a typical member of the M17 LAP family and may play an important role in free amino acid regulation in the parasite.

scholarly journals Analysis of molecular interactions of 8-gingerol compounds in Ginger (Zingiber officinale) as ACE Inhibitor

BIOEDUSCIENCE ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. 183-187
Author(s):  
Yohanes Bare ◽  
Mansur S ◽  
Aprianus Pani Pili ◽  
Maria Helvina
Keyword(s):  
Amino Acid ◽  
Hydrogen Bonds ◽  
Ace Inhibitor ◽  
Van Der Waals ◽  
Zingiber Officinale ◽  
Van Der Waals Forces ◽  
Amino Acid Residues ◽  
Protein Database ◽  
Discovery Studio ◽  
Software Analysis

Background: Hypertension is a disease with increasing characteristics of blood pressure. The ACE gene has a role in the conversion of ATI to ATII in hypertensive conditions. Healing is done by using the 8-gingerol content contained in ginger. The purpose of this study is to analyze the molecular interaction that occurs between 8-gingerol and ACE. Method: ACE model proteins (ID: 3bkk) were obtained from the Bank Data Protein database (PDB) through 8-gingerol ligands (CID: 168114) obtained from the PubChem database. ACE and 8-gingerol were docked by Discovery Study Client 4.1 software. Analysis of amino acid residues, binding energy, Van der Waals forces, and hydrogen bonds formed using Discovery Studio Client 4.1. Results: The interaction between 8-gingerol and ACE showed that there were seven amino acid residues that interacted with 8-gingerol, also found hydrogen bonds, hydrophobic and Van der Waals forces that strengthen and stabilize these bonds. Conclusion: the interaction of 8-ginger with the active side of ACE is determined as an ACE inhibitor, the inhibition is a significant effect on the obstruction of ACE conversion.

scholarly journals Docking Studies of Binding of Ethambutol to the C-Terminal Domain of the Arabinosyltransferase fromMycobacterium tuberculosis

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Guillermo Salgado-Moran ◽  
Rodrigo Ramirez-Tagle ◽  
Daniel Glossman-Mitnik ◽  
Samuel Ruiz-Nieto ◽  
Pran Kishore-Deb ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
In Silico ◽  
Docking Studies ◽  
Stable Complex ◽  
Amino Acid Residues ◽  
Terminal Domain ◽  
Docking Calculations

The binding of ethambutol to the C-terminal domain of the arabinosyltransferase fromMycobacterium tuberculosiswas studied. The analysis was performed using anin silicoapproach in order to find out, by docking calculations and energy descriptors, the conformer of Ethambutol that forms the most stable complex with the C-terminal domain of arabinosyltransferase. The complex shows that location of the Ethambutol coincides with the cocrystallization ligand position and that amino acid residues ASH1051, ASN740, ASP1052, and ARG1055 should be critical in the binding of Ethambutol to C-terminal domain EmbC.

scholarly journals A l-Lysine Transporter of High Stereoselectivity of the Amino Acid-Polyamine-Organocation (APC) Superfamily

2013 ◽  
Vol 289 (3) ◽  
pp. 1377-1387 ◽  
Author(s):  
Jagdeep Kaur ◽  
Elena Olkhova ◽  
Viveka Nand Malviya ◽  
Ernst Grell ◽  
Hartmut Michel
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Ligand Binding ◽  
Isothermal Titration Calorimetry ◽  
Functional Characterization ◽  
Homology Model ◽  
Docking Studies ◽  
Site Directed Mutagenesis ◽  
Titration Calorimetry ◽  
Amino Acid Residues

Membrane proteins of the amino acid-polyamine-organocation (APC) superfamily transport amino acids and amines across membranes and play an important role in the regulation of cellular processes. We report the heterologous production of the LysP-related transporter STM2200 from Salmonella typhimurium in Escherichia coli, its purification, and functional characterization. STM2200 is assumed to be a proton-dependent APC transporter of l-lysine. The functional interaction between basic amino acids and STM2200 was investigated by thermoanalytical methods, i.e. differential scanning and isothermal titration calorimetry. Binding of l-lysine to STM2200 in its solubilized monomer form is entropy-driven. It is characterized by a dissociation constant of 40 μm at pH 5.9 and is highly selective; no evidence was found for the binding of l-arginine, l-ornithine, l-2,4-diaminobutyric acid, and l-alanine. d-Lysine is bound 45 times more weakly than its l-chiral form. We thus postulate that STM2200 functions as a specific transport protein. Based on the crystal structure of ApcT (Shaffer, P. L., Goehring, A., Shankaranarayanan, A., and Gouaux, E. (2009) Science 325, 1010–1014), a proton-dependent amino acid transporter of the APC superfamily, a homology model of STM2200 was created. Docking studies allowed identification of possible ligand binding sites. The resulting predictions indicated that Glu-222 and Arg-395 of STM2200 are markedly involved in ligand binding, whereas Lys-163 is suggested to be of structural and functional relevance. Selected variants of STM2200 where these three amino acid residues were substituted using single site-directed mutagenesis showed no evidence for l-lysine binding by isothermal titration calorimetry, which confirmed the predictions. Molecular aspects of the observed ligand specificity are discussed.

scholarly journals Diarylalkanoids as Potent Tyrosinase Inhibitors from the Stems of Semecarpus caudata

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Phu H. Dang ◽  
Tho H. Le ◽  
Truong N. V. Do ◽  
Hai X. Nguyen ◽  
Mai T. T. Nguyen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inhibitory Activity ◽  
Spectroscopic Data ◽  
Data Interpretation ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Soluble Extract ◽  
Tyrosinase Inhibitory Activity ◽  
Ic50 Values ◽  
Tyrosinase Inhibitors

From a CHCl3-soluble extract of the stems of Semecarpus caudata (Anacardiaceae), two new diarylalkanoids, semedienone (1) and semetrienone (2), were isolated. Their structures were elucidated based on NMR spectroscopic data interpretation. These compounds possess strong tyrosinase inhibitory activity with the IC50 values of 0.033 and 0.11 μM, respectively. Docking studies of 1 and 2 with oxy-tyrosinase were carried out to analyze their interactions. Accordingly, semedienone (1) showed good interactions with the peroxide group and amino acid residues. The biosynthesis of the isolated diarylalkanoids was proposed.

scholarly journals Docking and dynamic simulation study of Crizotinib and Temozolomide drug with Glioblastoma and NSCLC target to identify better efficacy of the drug

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Saleena Younus ◽  
S. S. Vinod Chandra ◽  
Achuth Sankar S. Nair
Keyword(s):  
Hydrogen Bond ◽  
Amino Acid ◽  
Dynamic Simulation ◽  
Binding Sites ◽  
Protein Complexes ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Complex Energy ◽  
Stable Conformation ◽  
Least Energy

Abstract Background Crizotinib and Temozolomide are the two major chemotherapy drugs used for the treatment of cancers. Crizotinib is used as a target chemotherapy drug in many cancers. It mainly binds on the ATP binding regions of receptor tyrosine kinases (RTKs) targets and inhibits protein phosphorylation, which has already been reported. Temozolomide drug is known as the alkylating agent. Its mechanism of action is the methylation of DNA and thereby inhibiting DNA replication. However, the Temozolomide drug with protein level interaction of Glioblastoma Multiforme (GBM) and Non-small-cell lung carcinoma (NSCLC) of RTKs targets has not been reported so far. In the proposed work, we investigated the molecular level interaction of the Temozolomide drug in C-MET, C-ROS1, and ALK RTKs targets of GBM and NSCLC using an in silico study. We performed comparative analysis studies in both drugs' docked complexes based on their drug properties and complex energy (CE) to identify the better efficacy of the drug. Results From the docking studies, we could identify that the Temozolomide drug bounded protein complexes showed the least complex energy. The most stable complexes were identified from these docking studies by Molecular Dynamic simulation. In the proposed study, we found that the docked complex attained a stable conformation and least energy via solid hydrogen bond interactions between the amino acid residues and the drug at the binding sites of the proteins. The least energy and the hydrogen bond interaction of Temozolomide drug with the amino acid residues of the protein complexes of C-MET, C-ROS1 and ALK protein with their id name are: 2WGJ is − 11305.0830 (PRO1158, MET1160), 3ZBF is − 11,659.6814 (MET2029, GLU2027), and 2XP2 is − 11,734.7565 (ARG1275, ASP 1160, GLU1167). Conclusion Our studies revealed that the Temozolomide drug bounded protein complex showed the least energy when compared to Crizotinib. So it will give better interaction on the binding sites of proteins and thereby provide better inhibition in the treatment of target therapy of GBM and NSCLC.

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