scholarly journals Thrombolytic effect of Siddha herbal formulation Sikkanjar Manapagu using in-Silico model

2021 ◽  
Vol 12 (4) ◽  
pp. 908-911
Author(s):  
Panneerselvam N R ◽  
Anbarasan B ◽  
Subathra T
Keyword(s):  
In Silico ◽  
Zingiber Officinale ◽  
Docking Studies ◽  
Plasminogen Activation ◽  
Mentha Arvensis ◽  
Herbal Formulation ◽  
Thrombolytic Effect ◽  
Human Plasminogen ◽  
Active Amino Acid ◽  
Potential Methods

Background: Thromboembolic disorders are one of the important causes leading to death. In the Siddha system of medicine, many drugs have been mentioned in the literature and their thrombolytic potential needs to be scientifically evaluated. Aim: The study aims to perform the In Silico computational studies of Phytoconstituents of Siddha formulation Sikkanjar Manapagu (SM) to evaluate its thrombolytic potential. Methods: Autodock program was used for the molecular docking studies of the retrieved phytoconstituents such as Zingiberene, Gingerenone-A, 6 Gingerol of Zingiber officinale, Menthol, Luteolin, Citronellol of Mentha arvensis, Eugenol, Limonene, Myrcene, and Linalool of Citrus aurantium against target protein Human Plasminogen Activation Loop Peptide - PDB 4DCB. Results: A total of ten compounds were screened, of these Zingiberene, Menthol, Citronellol, Eugenol, Limonene, Myrcene, and Linalool showed high binding against active amino acid residue 195. Conclusion: Based on further experiments and clinical trials, the formulation Sikkanjar Manapagu could be proved to be effective in thrombolytic treatment.

scholarly journals Compounds of Citrus medica and Zingiber officinale for COVID-19 inhibition: in silico evidence for cues from Ayurveda

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
M. Haridas ◽  
Vijith Sasidhar ◽  
Prajeesh Nath ◽  
J. Abhithaj ◽  
A. Sabu ◽  
...  
Keyword(s):  
In Silico ◽  
Active Sites ◽  
Protein S ◽  
Zingiber Officinale ◽  
Nasal Carriage ◽  
Docking Studies ◽  
Spike Protein ◽  
Viral Shedding ◽  
In Silico Studies ◽  
Citrus Medica

Abstract Background The nasal carriage of SARS-CoV-2 has been reported as the key factor transmitting COVID-19. Interventions that can reduce viral shedding from the nasopharynx could potentially mitigate the severity of the disease and its contagiousness. Herbal formulation of Citrus medica and Zingiber officinale is recommended in an Ayurvedic text as a nasal rinse in the management of contagious fevers. These herbs are also indicated in the management of respiratory illnesses and have been attributed with activity against pathogenic organisms in other texts. Molecular docking studies of the phytocompounds of C. medica and Z. officinale were done to find out whether these compounds could inhibit the receptor binding of SARS-CoV-2 spike protein (S protein) as well as the angiotensin-converting enzyme 2 (ACE-2), as evidenced from their docking into binding/active sites. Results The proteins of SARS-CoV-2, essential for its entry into human cells and highly expressed in the goblet and ciliated cells of nasal epithelium, play a significant role in contagiousness of the virus. Docking studies indicated that the specific compounds present in C. medica and Z. officinale have significant affinity in silico to spike protein of virus and ACE-2 receptor in the host. Conclusion In silico studies suggest that the phytochemical compounds in C. medica and Z. officinale may have good potential in reducing viral load and shedding of SARS-CoV-2 in the nasal passages. Further studies are recommended to test its efficacy in humans for mitigating the transmission of COVID-19.

Mechanism of Human Plasminogen Activation by Streptokinase and Human Plasmin

1964 ◽  
Vol 11 (01) ◽  
pp. 085-093
Author(s):  
W. F Blatt ◽  
JL Gray ◽  
H Jensen
Keyword(s):  
Proteolytic Activity ◽  
Low Ph ◽  
Plasminogen Activation ◽  
Sensitive Tool ◽  
Human Plasminogen

SummaryA sensitive tool has been described for measuring fibrinolysis in reconstituted systems using thrombelastography. Activator mixtures with no appreciable proteolytic activity can similarly be tested in this system when the fibrinogen utilized has sufficient plasminogen present. Exposure of human plasminstreptokinase mixtures formed at pH 7.0 to acid conditions produced a striking loss of activator activity which could not be ascribed to low pH lability of the components, nor to plasmin action on the SK at pH 2.0. This is additional evidence for the hypothesis that human plasmin interacts with SK to form a complex capable of converting human and bovine plasminogen to plasmin.

In silico Discovery of Resveratrol Analogues as Potential Agents in Treatment of Metabolic Disorders

2019 ◽  
Vol 25 (35) ◽  
pp. 3776-3783
Author(s):  
Nebojša Pavlović ◽  
Maja Đanić ◽  
Bojan Stanimirov ◽  
Svetlana Goločorbin-Kon ◽  
Karmen Stankov ◽  
...  
Keyword(s):  
In Silico ◽  
Metabolic Disorders ◽  
Partial Agonist ◽  
Aqueous Solubility ◽  
Structural Similarity ◽  
Data Bank ◽  
Docking Studies ◽  
Binding Energies ◽  
Molegro Virtual Docker ◽  
Ppar Γ

Background: Resveratrol was demonstrated to act as partial agonist of PPAR-γ receptor, which opens up the possibility for its use in the treatment of metabolic disorders. Considering the poor bioavailability of resveratrol, particularly due to its low aqueous solubility, we aimed to identify analogues of resveratrol with improved pharmacokinetic properties and higher binding affinities towards PPAR-γ. Methods: 3D structures of resveratrol and its analogues were retrieved from ZINC database, while PPAR-γ structure was obtained from Protein Data Bank. Docking studies were performed using Molegro Virtual Docker software. Molecular descriptors relevant to pharmacokinetics were calculated from ligand structures using VolSurf+ software. Results: Using structural similarity search method, 56 analogues of resveratrol were identified and subjected to docking analyses. Binding energies were ranged from -136.69 to -90.89 kcal/mol, with 16 analogues having higher affinities towards PPAR-γ in comparison to resveratrol. From the calculated values of SOLY descriptor, 23 studied compounds were shown to be more soluble in water than resveratrol. However, only two tetrahydroxy stilbene derivatives, piceatannol and oxyresveratrol, had both better solubility and affinity towards PPAR-γ. These compounds also had more favorable ADME profile, since they were shown to be more metabolically stable and wider distributed in body than resveratrol. Conclusion: Piceatannol and oxyresveratrol should be considered as potential lead compounds for further drug development. Although experimental validation of obtained in silico results is required, this work can be considered as a step toward the discovery of new natural and safe drugs in treatment of metabolic disorders.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

2020 ◽  
Vol 17 (1) ◽  
pp. 40-50
Author(s):  
Farzane Kargar ◽  
Amir Savardashtaki ◽  
Mojtaba Mortazavi ◽  
Masoud Torkzadeh Mahani ◽  
Ali Mohammad Amani ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
In Silico ◽  
Alpha Helix ◽  
In Silico Analysis ◽  
Glycogen Storage ◽  
Docking Studies ◽  
Random Coil ◽  
Special Topic ◽  
Industrial Biotechnology ◽  
In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

Hetero-Tricyclic Lead Scaffold as Novel PDE5A Inhibitor for Antihypertensive Activity: In Silico Docking Studies

2019 ◽  
Vol 15 (4) ◽  
pp. 318-333
Author(s):  
Dipak P. Mali ◽  
Neela M. Bhatia
Keyword(s):  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Antihypertensive Activity ◽  
In Silico Docking ◽  
Π Stacking ◽  
Π Stacking Interaction ◽  
Nitrogen Heteroatom ◽  
Inhibitory Potential ◽  
Vlife Mds

Objective:To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies.Methods:In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software.Results:Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have shown one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds.Conclusion:In silico docking studies revealed that nitrogen-containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds have emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.

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