scholarly journals Antibacterial Activity of the Root Extracts of Garcinia Kola Against MDR Staphylococcus Aureus : Invitro and Insilico Studies

2021 ◽  
Author(s):  
Abdulbasit Haliru Yakubu ◽  
Muhammad Mustapha Muhammad
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Pocket ◽  
Docking Studies ◽  
Trna Synthetase ◽  
Root Extract ◽  
Antibacterial Drug ◽  
Economic Implication ◽  
Amino Acid Residues ◽  
Garcinia Kola ◽  
Staph Aureus

<p>MDR <b><i>Staphylococcus aureus</i></b> is an important bacteria with clinical and economic implication. Plants including Garcinia kola provides bioactive principles with diverse structural and biological features.. The n-Butanol fraction of <i>G.kola</i> root extract recorded the highest activity against MDR staph aureus (18.50±0.41) compared to the chloroform (10.00±2.12) and methanol (8.166±0.62) extarct, with no activity recorded with the n-Hexane extract. Analysis of this fraction on GC-MS recorded 14 phytoconstituents with varying structural composition; containing important scaffolds & motifs of benzoquinone, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/imidazo[1,2-a]pyridine">imidazo[1,2-a]pyridine</a>, Chlorocarbazole and azetidine that present key pharmaceuticals as antibiotic and for drug development. Further inslico molecular docking studies of these compounds on antibacterial drug target; Tyrosyl-tRNA synthetase (PDB 1JIJ) from MDR staph aureus was documented. 9 compounds (CID_619544, CID_619583, CID_5732, CID_616643, CID_622021, CID_ 616496, CID_590350, CID_16486 and CID_66747) had good binding scores ranging from -4.63 to -7.08 kcal/mol; with CID_590350 having the highest score. The compounds formed various bonding with the 1JIJ amino acid residues including H-bond, van der waal and π interactions. CID_16486 and CID_66747 bind to the most active binding pocket (Drug score: 0.82 &0.72) while CID_619583 tend to bind outside the active binding pocket. They also have good pharmacokinetic and toxicity profile. Therefore, these compounds are considered as suitable prospective antibiotics against MDR <b><i>Staphylococcus aureus</i></b> after successful <i>invitro</i> and <i>insilico</i> experimental validation.<b></b></p>

scholarly journals Antibacterial Activity of the Root Extracts of Garcinia Kola Against MDR Staphylococcus Aureus : Invitro and Insilico Studies

2021 ◽  
Author(s):  
Abdulbasit Haliru Yakubu ◽  
Muhammad Mustapha Muhammad
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Pocket ◽  
Docking Studies ◽  
Trna Synthetase ◽  
Root Extract ◽  
Antibacterial Drug ◽  
Economic Implication ◽  
Amino Acid Residues ◽  
Garcinia Kola ◽  
Staph Aureus

<p>MDR <b><i>Staphylococcus aureus</i></b> is an important bacteria with clinical and economic implication. Plants including Garcinia kola provides bioactive principles with diverse structural and biological features.. The n-Butanol fraction of <i>G.kola</i> root extract recorded the highest activity against MDR staph aureus (18.50±0.41) compared to the chloroform (10.00±2.12) and methanol (8.166±0.62) extarct, with no activity recorded with the n-Hexane extract. Analysis of this fraction on GC-MS recorded 14 phytoconstituents with varying structural composition; containing important scaffolds & motifs of benzoquinone, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/imidazo[1,2-a]pyridine">imidazo[1,2-a]pyridine</a>, Chlorocarbazole and azetidine that present key pharmaceuticals as antibiotic and for drug development. Further inslico molecular docking studies of these compounds on antibacterial drug target; Tyrosyl-tRNA synthetase (PDB 1JIJ) from MDR staph aureus was documented. 9 compounds (CID_619544, CID_619583, CID_5732, CID_616643, CID_622021, CID_ 616496, CID_590350, CID_16486 and CID_66747) had good binding scores ranging from -4.63 to -7.08 kcal/mol; with CID_590350 having the highest score. The compounds formed various bonding with the 1JIJ amino acid residues including H-bond, van der waal and π interactions. CID_16486 and CID_66747 bind to the most active binding pocket (Drug score: 0.82 &0.72) while CID_619583 tend to bind outside the active binding pocket. They also have good pharmacokinetic and toxicity profile. Therefore, these compounds are considered as suitable prospective antibiotics against MDR <b><i>Staphylococcus aureus</i></b> after successful <i>invitro</i> and <i>insilico</i> experimental validation.<b></b></p>

Antibacterial Activity of the Root Extracts of Garcinia Kola Against MDR Staphylococcus Aureus : Invitro and Insilico Studies

2021 ◽  
Author(s):  
Abdulbasit Haliru Yakubu ◽  
Muhammad Mustapha Muhammad
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Target ◽  
Binding Pocket ◽  
Trna Synthetase ◽  
Root Extract ◽  
Antibacterial Drug ◽  
Economic Implications ◽  
Garcinia Kola ◽  
Staph Aureus ◽  
Butanol Fraction

Multi-Drug Resistant (MDR) Staphylococcus aureus is an important bacteria with clinical and economic implications. Plants including Garcinia kola provides bioactive principles with diverse structural and biological features. Tyrosyl-tRNA synthetase (TyrRS) is targeted in antibacterial drug discovery as its implicated in bacterial protein synthesis. The n-Butanol fraction of Garcinia kola root extract recorded the highest activity against MDR staph aureus (18.50±0.41) compared to the chloroform (10.00±2.12) and methanol (8.16±0.62) extract, with no activity recorded with the n-Hexane extract. Analysis of the n-Butanol fraction on GC-MS recorded 14 phytoconstituents with varying structural composition; containing important scaffolds & motifs of benzoquinone, imidazole[1,2-a]pyridine, chlorocarbazole and azetidine that present key pharmaceuticals as antibiotic and for drug development. Further insilico molecular docking studies of these compounds on antibacterial drug target; Tyrosyl-tRNA synthetase (PDB 1JIJ) from MDR staph aureus were documented. Nine (9) compounds had good binding scores ranging from -4.63 to -7.08 kcal/mol; with CID_590350 having the highest score. The compounds formed various bonding with the 1JIJ amino acid residues including H-bond, van der waal and π interactions. Five (5) compounds; CID_619583 (9,9-Dichloro-9-silafluorene), CID_5732 (Zolpidem), CID_616643 (Pyridazine-3,5-dicarbonitrile, 1,6-dihydro-4-amino-6-imino-1-(2-nitrophenyl)), CID_16486 ((S)-(-)-2-Azetidinecarboxlic acid) and CID_66747 (2-Hydroxyethyl benzoate) showed favorable ADME properties, while their MD stimulation analysis revealed stable binding capabilities with the drug target. CID_16486 and CID_66747 bind to the most active binding pocket (Drug score: 0.82 and 0.72) while CID_619583 tends to bind outside the active binding pocket. Therefore, these compounds from the root of Garcinia kola are considered as suitable prospective bioactive compounds against MDR Staphylococcus aureus after successful in vitro and in silico experimental validation.

scholarly journals Expanding the Scope of Orthogonal Translation with Pyrrolysyl-tRNA Synthetases Dedicated to Aromatic Amino Acids

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4418
Author(s):  
Hsueh-Wei Tseng ◽  
Tobias Baumann ◽  
Huan Sun ◽  
Yane-Shih Wang ◽  
Zoya Ignatova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Aromatic Amino Acids ◽  
Binding Pocket ◽  
Trna Synthetase ◽  
Rational Approach ◽  
Translation Efficiency ◽  
Amino Acid Residues ◽  
Trna Synthetases ◽  
Methanosarcina Mazei ◽  
Genetic Code Expansion

In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNAPyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants have been developed during the last decade, enabling a substantial genetic code expansion, mainly with aliphatic pyrrolysine analogs. However, comparatively less progress has been made to expand the substrate range of MmPylRS towards aromatic amino acid residues. Therefore, we set to further expand the substrate scope of orthogonal translation by a semi-rational approach; redesigning the MmPylRS efficiency. Based on the randomization of residues from the binding pocket and tRNA binding domain, we identify three positions (V401, W417 and S193) crucial for ncAA specificity and enzyme activity. Their systematic mutagenesis enabled us to generate MmPylRS variants dedicated to tryptophan (such as β-(1-Azulenyl)-l-alanine or 1-methyl-l-tryptophan) and tyrosine (mainly halogenated) analogs. Moreover, our strategy also significantly improves the orthogonal translation efficiency with the previously activated analog 3-benzothienyl-l-alanine. Our study revealed the engineering of both first shell and distant residues to modify substrate specificity as an important strategy to further expand our ability to discover and recruit new ncAAs for orthogonal translation

scholarly journals Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2815 ◽  
Author(s):  
Pisano ◽  
Kumar ◽  
Medda ◽  
Gatto ◽  
Pal ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Structural Features ◽  
Docking Studies ◽  
Trna Synthetase ◽  
Hydroxyl Groups ◽  
Bacterial Strains ◽  
Active Compounds ◽  
Molecular Docking Studies

Antibiotic resistance is one of the main public health concerns of this century. This resistance is also associated with oxidative stress, which could contribute to the selection of resistant bacterial strains. Bearing this in mind, and considering that flavonoid compounds are well known for displaying both activities, we investigated a series of hydroxy-3-arylcoumarins with structural features of flavonoids for their antibacterial activity against different bacterial strains. Active compounds showed selectivity against the studied Gram-positive bacteria compared to Gram-negative bacteria. 5,7-Dihydroxy-3-phenylcoumarin (compound 8) displayed the best antibacterial activity against Staphylococcus aureus and Bacillus cereus with minimum inhibitory concentrations (MICs) of 11 g/mL, followed by Staphylococcus aureus (MRSA strain) and Listeria monocytogenes with MICs of 22 and 44 g/mL, respectively. Moreover, molecular docking studies performed on the most active compounds against Staphylococcus aureus tyrosyl-tRNA synthetase and topoisomerase II DNA gyrase revealed the potential binding mode of the ligands to the site of the appropriate targets. Preliminary structure–activity relationship studies showed that the antibacterial activity can be modulated by the presence of the 3-phenyl ring and by the position of the hydroxyl groups at the coumarin scaffold.

The Discovery of Antibacterial Natural Compound Based on Peptide Deformylase

2018 ◽  
Vol 21 (4) ◽  
pp. 292-297 ◽  
Author(s):  
Li Liang ◽  
Qianqian Zhou ◽  
Zhixiang Hao ◽  
Fanfan Wang ◽  
Yasheng Zhu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
Peptide Deformylase ◽  
Antibacterial Drug ◽  
Binding Interaction ◽  
Docking Score ◽  
Human Infections ◽  
Antibacterial Drug Target ◽  
Mic Value

Background: In recent years, Staphylococcus aureus have developed resistance to medicines used for the treatment of human infections. Therefore, the search for antibacterial agents of high potency against Staphylococcus aureus is of great concern. Peptide deformylase (PDF), a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, has been considered to be an important antibacterial drug target. Objective: To discover novel antibacterial drugs based on Staphylococcus aureus peptide deformylase. Method: PDF-based virtual screening of compounds from Traditional Chinese Medicine Database@Taiwan was performed by Sybyl X2.1 Surflex dock software. Compounds which possess high docking score were used for the following antibacterial experiments to evaluate their antibacterial activities. Kanamycin was also used in the antibacterial experiment as a control substance in the assay. Furthermore, molecular docking studies was applied to elucidate binding interaction between some compounds and PDF. In silico pharmacokinetic and toxicity prediction was explored to explain the reasons why these compounds might stand good chance of providing some pharmaceutical benefits. Results: Gentiopicroside, protosappanin B, dihydromyricetin and cryptochlorogenic acid with high docking score were used for our subsequent antibacterial assays. The Minimum Inhibitory Concentration (MIC) of kanamycin and gentiopicroside were 0.008 mg·mL-1 and 0.431 mg·mL-1, respectively, other three compounds, protosappanin B, dihydromyricetin and cryptochlorogenic acid have close MIC value of 0.50 mg·mL-1. Conclusion: Dihydromyricetin, with the MIC value of 0.50 mg·mL-1 and relatively high drug score of 0.82, may serve as a novel antibacterial lead compound.

scholarly journals Synthesis, Properties and Antimicrobial Activity of 5-Trifluoromethyl-2-formylphenylboronic Acid

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 799 ◽  
Author(s):  
Agnieszka Adamczyk-Woźniak ◽  
Jan T. Gozdalik ◽  
Dorota Wieczorek ◽  
Izabela D. Madura ◽  
Ewa Kaczorowska ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Candida Albicans ◽  
Bacillus Cereus ◽  
Title Compound ◽  
Phenylboronic Acid ◽  
Binding Pocket ◽  
Docking Studies ◽  
Trna Synthetase

2-Formylphenylboronic acids display many interesting features, not only from synthetic but also from an application as well as structural points of view. 5-Trifluoromethyl-2-formyl phenylboronic acid has been synthesized and characterized in terms of its structure and properties. The presence of an electron-withdrawing substituent results in a considerable rise in the acidity in comparison with its analogues. In some solutions, the title compound isomerizes with formation of the corresponding 3-hydroxybenzoxaborole. Taking into account the probable mechanism of antifungal action of benzoxaboroles, which blocks the cytoplasmic leucyl-tRNA synthetase (LeuRS) of the microorganism, docking studies with the active site of the enzymes have been carried out. It showed possible binding of the cyclic isomer into the binding pocket of Candida albicans LeuRS, similar to that of the recently approved benzoxaborole antifungal drug (AN2690, Tavaborole, Kerydin). In case of Escherichia coli LeuRS, the opened isomer displays a much higher inhibition constant in comparison with the cyclic one. The antimicrobial activity of the title compound was also investigated in vitro, showing moderate action against Candida albicans. The compound reveals higher activity against Aspergillus niger as well as bacteria such as Escherichia coli and Bacillus cereus. In case of Bacillus cereus, the determined Minimum Inhibitory Concentration (MIC) value is lower than that of AN2690 (Tavaborole). The results confirm potential of 2-formylphenylboronic acids as antibacterial agents and give a hint of their possible mechanism of action.

Assessment of the Multifactorial Effect on Antimicrobial Sensitivity in Positive Staphylococcus Aureus Clinical Isolates from Assir Region, Saudi Arabia

2012 ◽  
Vol 13 (2) ◽  
pp. 152-159 ◽  
Author(s):  
Nazar M Abdalla ◽  
Waleed O Haimour ◽  
Amani A Osman ◽  
Hassan Abdul Aziz
Keyword(s):  
Staphylococcus Aureus ◽  
Saudi Arabia ◽  
Culture Media ◽  
Meca Gene ◽  
Laboratory Data ◽  
Age Groups ◽  
Clinical Isolates ◽  
Diabetic Patients ◽  
Staph Aureus ◽  
Antimicrobial Sensitivity

General objectives: This study aimed at assessment of factors affecting antimicrobial sensitivity in Staphylococcus aureus clinical isolates from Assir region, Saudi Arabia. Materials and Methods: In this study, eighty one patients presented with Staph. aureus infections either nosocomial or community acquired infections were involved by collecting nasal swabs from them at Aseer Central Hospital General Lab. These patients were from all age groups and from males and females during the period of Jan 2011- Jun 2011. These samples were undergone variable laboratory procedures mainly; bactech, culture media, antibiotics sensitivity test using diffusion disc test (MIC) and molecular (PCR) for detection of mec A gene. Clinical and laboratory data were recorded in special formats and analyzed by statistical computer program (SPSS). Results: Showed that; Descriptive and analytical statistical analysis were performed and final results were plotted in tables. In Staph aureus MecA gene positive cases (50) showed: Oxacillin/ Mithicillin, Ciprofloxacin and Fusidin resistant in diabetic patients were 13, 26.0%, 9, 18% and 7, 14% respectively and in non diabetic patients were 37, 74.0%, 22, 44% and 20, 40% respectively. While no sensitivity in diabetic and non diabetic patients using Oxacillin/ Mithicillin. In Staph aureus MecA gene negative cases (31) showed: Oxacillin/ Mithicillin, sensitivity in diabetic patients (5, 16.1%) and in non diabetic were (26, 83.9%). While no resistant in diabetic and non diabetic patients. In Ciprofloxacin and Fusidin resistant in diabetic patients were 1, 3.2% and 1, 3.2% respectively and in non diabetic patients were 12, 38.7% and 7, 22.6%respectively. Erythromycin in Staph aureus ( MecA gene) positive cases (50) showed: resistant in age (0-15) years were (5, 10%), (16-50) years were (16, 32%) and ( ›50 years) were (12, 24%). Erythromycin in Staph aureus (MecA gene) negative cases (31) showed: resistant in age (0-15) years were (6, 19.3%), (16-50) years were (5, 16.1%) and ( ›50 years) were (3, 9.7%). Conclusion: Drugs resistance is a major progressive multifactorial problem facing the treatment of Staph aureus infections. DOI: http://dx.doi.org/10.3329/jom.v13i2.12750 J Medicine 2012; 13 : 152-159

Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Sowmya Suri ◽  
Rumana Waseem ◽  
Seshagiri Bandi ◽  
Sania Shaik
Keyword(s):  
Molecular Docking ◽  
3D Model ◽  
Structural Features ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Cyclin Dependent Kinase ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Molecular Docking Studies ◽  
Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

In Silico Studies on Anti-Stress Compounds of Ethanolic Root Extract of Hemidesmus indicus L.

2020 ◽  
Vol 21 (6) ◽  
pp. 502-515
Author(s):  
Jayasimha R. Daddam ◽  
Basha Sreenivasulu ◽  
Katike Umamahesh ◽  
Kotha Peddanna ◽  
Dowlathabad M. Rao
Keyword(s):  
Conventional Medicine ◽  
Herbal Medicines ◽  
Ethanolic Extract ◽  
Data Bank ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Alternative Methods ◽  
Root Extract ◽  
Hemidesmus Indicus ◽  
In Silico Studies

Background: Alternative medicine is available for those diseases which cannot be treated by conventional medicine. Ayurveda and herbal medicines are important alternative methods in which the treatment is done with extracts of different medicinal plants. This work is concerned with the evaluation of anti-stress bioactive compounds from the ethanolic root extract of Hemidesmus indicus. Methods: Gas chromatography and Mass Spectrum studies are used to identify the compounds present in the ethanolic extract based on the retention time, area. In order to perform docking studies, Vasopressin model is generated using modeling by Modeller 9v7. Vasopressin structure is developed based on the crystal structure of neurophysin-oxytocin from Bos taurus (PDB ID: 1NPO_A) collected from the PDB data bank. Using molecular dynamics simulation methods, the final predicted structure is obtained and further analyzed by verifying 3D and PROCHECK programs, confirmed that the final model is reliable. The identified compounds are docked to vasopressin for the prediction of anti-stress activity using GOLD 3.0.1 software. Results: The predicted model of Vasopressin structure is stabilized and confirmed that it is a reliable structure for docking studies. The results indicated ARG4, THR7, ASP9, ASP26, ALA32, ALA 80 in Vasopressin are important determinant residues in binding as they have strong hydrogen bonding with phytocompounds. Among the 21 phytocompounds identified and docked, molecule Deoxiinositol, pentakis- O-(trimethylsilyl) showed the best docking results with Vasopressin. Conclusion: The identified compounds were used for anti-stress activity by insilico method with Vasopressin which plays an important role in causing stress and hence selected for inhibitory studies with phytocompounds. The phytocompounds are inhibiting vasopressin through hydrogen bodings and are important in protein-ligand interactions. Docking results showed that out of twenty-one compounds, Deoxiinositol, pentakis-O-(trimethylsilyl) showed best docking energy to the Vasopressin.

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