Marine Streptomyces-derived Antibacterial Compound [2, 4-Dichloro-5-sulfamoyl benzoic acid] for MRSA and VRE Strains

2016 ◽  
Vol 9 (5) ◽  
pp. 3458-3461
Author(s):  
Kannabiran K. ◽  
Benita Mercy Rajan
Keyword(s):  
Folic Acid ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
Benzoic Acid ◽  
Inhibition Constant ◽  
Ligand Docking ◽  
Drug Candidate ◽  
Synthesis Inhibitor ◽  
Carcinogenic Effect ◽  
Dps Protein

The aim of the present study was to predict the interaction of 4-dichloro-5-sulfamoyl benzoic acid (DSBA) derived from Streptomyces sp. VITBRK3 with the drug target enzymes of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococci (VRE) strains procured from ATCC. Two proteins dihydropteroate synthetase (DPS) and dihydrofolate reductase (DFR) were chosen as drug targets. The well-known folic acid synthesis inhibitor amino salicylic acid (ASA) was taken as a positive control. AutoDock 4.2.1 was used to perform the protein-ligand docking analysis. DSBA showed least binding energy of –6.99 kcal/mol and inhibition constant of 7.5 µM and formed 8 hydrogen bonds with DFR. DSBA showed least binding energy of -5.6 kcal/mol and inhibition constant of 78.58 µM and formed 7 hydrogen bonds with DPS.  ASA showed the binding energy of –4.97 kcal/mol, and inhibition constant of 225.9 µM and formed 5 hydrogen bonds with DPS protein. It showed the binding energy of          –4.68 kcal/mol, and inhibition constant of 371.32 µM and formed 4 hydrogen bonds with DFR protein. DSBA has qualified CMC rule, lead like rule and Lipinski’s rule of five. The compound DSBA does not possess any carcinogenic effect in rat or mouse model. Osiris Property Explorer analysis suggested that, DSBA does not possess any major side effects and is a suitable drug candidate. Pre ADMET analysis also suggests that, the lead compound, DSBA is a suitable drug candidate. The results of this study suggest that the antimicrobial activity of DSBA against MRSA and VRE strains is due to its inhibition over bacterial cell wall folic acid biosynthesis.

scholarly journals Multi-Targeted Molecular Docking, Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5957
Author(s):  
Syed Amir Ashraf ◽  
Abd Elmoneim O. Elkhalifa ◽  
Khalid Mehmood ◽  
Mohd Adnan ◽  
Mushtaq Ahmad Khan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Abscisic Acid ◽  
Molecular Docking ◽  
Binding Energy ◽  
Age Groups ◽  
Ppar Gamma ◽  
Inhibition Constant ◽  
Drug Candidate ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.

IN VITRO AND IN SILICO ALPHA-AMYLASE INHIBITION POTENTIAL (ANTI-DIABETIC ACTIVITY) OF PSEUDERANTHEMUM BICOLOR (SIMS) RADIK

2020 ◽  
pp. 157-161
Author(s):  
RAMESH BS ◽  
LOKESH RAVI
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
Ethyl Acetate ◽  
Bioactive Compounds ◽  
Methyl Ether ◽  
Docking Study ◽  
Alpha Amylase ◽  
Ligand Docking ◽  
Standard Drug ◽  
Reference Drug

Objective: Aim of this study is to evaluate theanti-diabetic activity of Pseuderanthemum bicolor commonly called limang-sugat by inhibiting alpha-amylase protein. Methods: Leaves of P. bicolor were extracted with methanol, chloroform, and ethyl acetate. The extracts were subjected for alpha-amylase inhibition assay and gas chromatography–mass spectrometry (GC–MS) analysis. Phytochemical compounds identified by GC-MS were subjected for protein-ligand docking study against alpha-amylase protein. Acarbose was used as a positive standard drug. Results: The major bioactive compounds obtained from methanol, chloroform, and ethyl acetate extracts were 1,6;2,3-Dianhydro-4-Deoxy-Beta-D-Ribo-Hexopyranose, Pseduosarsasapogenin-5,20-Dien, methyl ether/Hexatriacontane, Di-N-decylsulfone/Octadecanal, and squalene, respectively. A total of 19 secondary metabolites were subjected for protein–ligand docking study against the alpha-amylase protein. The reference drug acarbose demonstrated binding energy of −7.8 Kcal/mol and formed 20 hydrogen bonds with the enzyme. Acarbose signified high polar interaction with the amylase enzyme. Among the 19 test ligands, “2,2-Dibromocholestanone” from ethyl acetate extract exemplified the highest binding energy of −9.3 Kcal/mol. The next highest remarkable inhibition was showed by “Pseduosarsasapogenin-5,20-Dien Methyl Ether” present in the methanol extract, with a binding energy of -9.3 Kcal/mol with the formation of 2 hydrogen bonds. Conclusion: From the result, it could be concluded that the P. bicolor leaves contain various bioactive compounds which are considered as a good anti-diabetic drug.

scholarly journals ANTI-PARKINSON POTENTIAL OF PERSEA AMERICANA SEED EXTRACTS THROUGH IN-SILICO DOCKING STUDY

2020 ◽  
pp. 152-155
Author(s):  
RACHAEL EVANGELINE ◽  
NIHAL AHMED
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Water Extract ◽  
Docking Study ◽  
Persea Americana ◽  
Ligand Docking ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Free Binding Energy

Objective: The aim of this study is to investigate the potential of Persea americana extracts for their Anti-Parkinson application through an in-silico docking study. Methods: PubChem and protein data bank databases were used to retrieve 3D structures. AutoDock4 was used to perform protein-ligand docking analysis. PyMOL was used to visualize the docking results. Results: Among the 30 ligand, the highest affinity was demonstrated by Hesperidin with a free binding energy of −6.8 kcal/mol and formation of five hydrogen bonds. The second highest significance was demonstrated by Biphenyl 4-(4-diethylaminobenzylidenamino) with a free binding energy of −5.9 kcal/mol with the formation of 2 hydrogen bonds. Among the three sets of phytochemicals from different solvent extracts, water extract demonstrated the highest potential as Anti-Parkinson active. Conclusion: P. americana extracts were analyzed for their Anti-Parkinson potential, and among the three extracts, the aqueous extract was predicted to have significant Anti-Parkinson potential, based on in silico docking analysis, due to the presence of active phytochemicals such as Hesperidin and others.

Molecular Docking Studies on the Anti-Fungal Activity of Allium Sativum (Garlic) Against Mucormycosis (Black Fungus) by BIOVIA Discovery Studio Visualizer 21.1.0.0

2021 ◽  
Author(s):  
Shaweta Sharma ◽  
Akhil Sharma ◽  
Utsav Gupta
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
Docking Studies ◽  
Binding Energies ◽  
Inhibition Constant ◽  
Beta Glucan ◽  
Glucan Synthase ◽  
Fungal Protein ◽  
Discovery Studio ◽  
Black Fungi

Abstract Background: The COVID-19 pandemic is a major concern. However, its association and rising cases of mucormycosis, also known as black fungus make the scenario even more troublesome. In addition, no specific medication against mucormycosis/black fungus makes things even worse.Objective: Garlic phytoconstituents have shown remarkable antifungal properties against various fungal species in various studies. Thus, the objective of the study was to check the potency of garlic phytoconstituents against the 1,3-beta-glucan synthase fungal protein using in-silico methods.Method: Auto Dock was used to evaluate selected garlic phytochemical molecules against 1,3-beta-glucan synthase fungal protein, and Discovery studio visualizer was used to create 3D and 2D interaction photos.Results: Five out of 9 phytoconstituents were found to form conventional hydrogen bonds, and only alliin formed the highest number of hydrogen bonds. However, the binding energy and inhibition constant of all nine phytoconstituents were determined. Interestingly, Z-ajoene showed the lowest binding energy of -5.07 kcal/mol and inhibition constant of 192.57µM.Conclusion: The results of our investigation suggested that garlic phytochemicals can have a good impact against black fungi, pertaining to the significant binding energies of phytoconstituents during blind docking. Specifically, Z-ajoene could be a good alternate against black fungi. However, detailed research is required to explore the antifungal activity of garlic against mucormycosis.

scholarly journals Molecular Docking studies on the Anti-fungal activity of Allium sativum (Garlic) against Mucormycosis (black fungus) by BIOVIA discovery studio visualizer 21.1.0.0

2021 ◽  
pp. 028-032
Author(s):  
Sharma Shaweta ◽  
Sharma Akhil ◽  
Gupta Utsav
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
Docking Studies ◽  
Binding Energies ◽  
Inhibition Constant ◽  
Beta Glucan ◽  
Glucan Synthase ◽  
Fungal Protein ◽  
Discovery Studio ◽  
Black Fungi

Background: The COVID-19 pandemic is a major concern. However, its association and rising cases of mucormycosis, also known as black fungus make the scenario even more troublesome. In addition, no specific medication against mucormycosis/black fungus makes things even worse. Objective: Garlic phytoconstituents have shown remarkable antifungal properties against various fungal species in various studies. Thus, the objective of the study was to check the potency of garlic phytoconstituents against the 1,3-beta-glucan synthase fungal protein using in-silico methods. Method: Auto Dock was used to evaluate selected garlic phytochemical molecules against 1,3-beta-glucan synthase fungal protein, and Discovery studio visualizer was used to create 3D and 2D interaction photos. Results: Five out of 9 phytoconstituents were found to form conventional hydrogen bonds, and only alliin formed the highest number of hydrogen bonds. However, the binding energy and inhibition constant of all nine phytoconstituents were determined. Interestingly, Z-ajoene showed the lowest binding energy of -5.07 kcal/mol and inhibition constant of 192.57µM. Conclusion: The results of our investigation suggested that garlic phytochemicals can have a good impact against black fungi, pertaining to the significant binding energies of phytoconstituents during blind docking. Specifically, Z-ajoene could be a good alternate against black fungi. However, detailed research is required to explore the antifungal activity of garlic against mucormycosis.

scholarly journals ANTI-METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS POTENTIAL OF PHYTOCHEMICALS IN TERMINALIA CATAPPA AND THEIR PROPOSED IN SILICO MECHANISM OF ACTION

2019 ◽  
pp. 133-137
Author(s):  
LOKESH RAVI ◽  
DIVYA JINDAM ◽  
SUGANYA KUMARESAN ◽  
VENKATESH SELVARAJ ◽  
JAYARAMA REDDY
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
Mechanism Of Action ◽  
In Silico ◽  
Ethanol Extract ◽  
Docking Study ◽  
Ligand Docking ◽  
Methicillin Resistant ◽  
Antibacterial Potential

Objective: The objective of this study was to investigate the antibacterial potential of leaves of this Terminalia catappa and identify the mechanism of action for those phytochemicals present in this leaves. Methods: Phytochemicals were extracted using maceration and the extracts were analyzed using gas chromatography–mass spectrometry (GC-MS) to identify the chemical structure. Antibacterial potential was evaluated using agar well diffusion. The phytochemicals were subjected to in silico protein–ligand docking study to identify the mechanism of action. Results: In vitro antibacterial study demonstrated that the ethanol extract of the leaves has significant antibacterial activity against Staphylococcus aureus (SA) and methicillin-resistant SA (MRSA) with a zone of inhibition of 16 mm and 18 mm, respectively, at a concentration of 2 mg/ml. The chloroform and hexane extracts of the leaves did not demonstrate any significant activity. Based on GC-MS analysis and literature review, 12 phytochemicals were identified to be present in the ethanol extract of the T. catappa leaves. These molecules were subjected to in silico protein–ligand docking study against common drug target proteins of SA and MRSA. Among the studied ligands, granatin A demonstrated the highest significance to inhibit topoisomerase IV with a binding energy of −11.3 kcal/mol and produced 7 hydrogen bonds, followed by punicalin with −10.7 kcal/mol binding energy toward penicillin-binding protein 2a with 6 hydrogen bonds. Conclusion: Phytochemicals of T. catappa demonstrates significant drug ability potential against drug-resistant MRSA pathogen and demands further investigation on their individual activity and mechanism.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

scholarly journals Molecular Dynamics Simulations for Effects of Fluoropolymer Binder Content in CL-20/TNT Based Polymer-Bonded Explosives

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4876
Author(s):  
Shenshen Li ◽  
Jijun Xiao
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Correlation Function ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
Bond Length ◽  
Pair Correlation Function ◽  
Pair Correlation ◽  
Binder Content ◽  
Polymer Bonded Explosives

In order to better understand the role of binder content, molecular dynamics (MD) simulations were performed to study the interfacial interactions, sensitivity and mechanical properties of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane/2,4,6-trinitrotoluene (CL-20/TNT) based polymer-bonded explosives (PBXs) with fluorine rubber F2311. The binding energy between CL-20/TNT co-crystal (1 0 0) surface and F2311, pair correlation function, the maximum bond length of the N–NO2 trigger bond, and the mechanical properties of the PBXs were reported. From the calculated binding energy, it was found that binding energy increases with increasing F2311 content. Additionally, according to the results of pair correlation function, it turns out that H–O hydrogen bonds and H–F hydrogen bonds exist between F2311 molecules and the molecules in CL-20/TNT. The length of trigger bond in CL-20/TNT were adopted as theoretical criterion of sensitivity. The maximum bond length of the N–NO2 trigger bond decreased very significantly when the F2311 content increased from 0 to 9.2%. This indicated increasing F2311 content can reduce sensitivity and improve thermal stability. However, the maximum bond length of the N–NO2 trigger bond remained essentially unchanged when the F2311 content was further increased. Additionally, the calculated mechanical data indicated that with the increase in F2311 content, the rigidity of CL-20/TNT based PBXs was decrease, the toughness was improved.

scholarly journals Crystal structure of 2-{[1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yloxy]carbonyl}benzoic acid

2014 ◽  
Vol 70 (12) ◽  
pp. o1237-o1238
Author(s):  
Hafiz Abdullah Shahid ◽  
Sajid Jahangir ◽  
Syed Adnan Ali Shah ◽  
Hamizah Mohd Zaki ◽  
Humera Naz
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Benzoic Acid ◽  
Dihedral Angle ◽  
Title Compound ◽  
Compound C

In the title compound, C15H15N3O6, the dihedral angle between the planes of the benzene and imidazole rings is 34.93 (10)°. An intramolecular C—H...O hydrogen bond is observed. In the crystal, O—H...N hydrogen bonds link the molecules into chains parallel to thecaxis.

scholarly journals MOLECULAR DOCKING TERPINEN-4-OL SEBAGAI ANTIINFLAMASI PADA ATEROSKLEROSIS SECARA IN SILICO

Jurnal Kimia ◽  
2019 ◽  
pp. 221
Author(s):  
N. M. P. Susanti ◽  
N. P. L. Laksmiani ◽  
N. K. M. Noviyanti ◽  
K. M. Arianti ◽  
I K. Duantara
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Endothelial Dysfunction ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Inflammatory Process ◽  
Mapk Pathway ◽  
Chronic Inflammatory Disease ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

Atherosclerosis is a chronic inflammatory disease that begins with endothelial dysfunction, it caused fat accumulation and plaque growth in the inner arteries walls. Endothelial dysfunction will activate the Mitogen Activated Protein Kinase (MAPK) pathway involving ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, as well as the Nuclear Factor Kappa B (NF-kB) pathway involving IKK proteins. Terpinen-4-ol is constituent found in the bangle rhizome. The purpose of this study were to determine the affinity and mechanisms of terpinen-4-ol against ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins as anti-inflammatory in atherosclerosis performed using molecular docking method. The study was conducted exploratively with several steps such as preparation and optimization of terpinen-4-ol structure, preparation of 3D ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, validation method of molecular docking, and docking terpinen-4-ol in these proteins. The docking result are assessed from the binding energy and hydrogen bonds formed between terpinen-4-ol and proteins. The smaller value of binding energy terpinen-4-ol with target proteins showed the complex that form more stable. The result showed that terpinen-4-ol and has activity in inhibiting the inflammatory process because it is able to disturb ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins with respective bond energy values -5,12; -5,24; -5,08; -5,88; and -4,99 Kcal/mol. The molecular mechanism in inhibiting the activity of ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins is through the formation of hydrogen bonds in these proteins. These results show that terpinen-4-ol have the potential to inhibit inflammatory process and the formation of atherosclerotic plaque can be obstructed. Keywords : atherosclerosis, terpinen-4-ol, molecular docking, in silico

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