Plant secondary metabolites have provided important bioactive principles for developing new lead compounds. Within their confinement, they exhibit unique chemical diversity, which influences their diverse biological properties. The Vitaceae family is known for its potent antioxidant and antibacterial phytoconstituents, among other biological properties. Cyphostemma adenocaule is one of the family members explored for its ethnomedicinal properties. This study undertook the evaluation of the phytochemical, antioxidant, and antibacterial properties of the root extract of Cyphostemma adenocaule. Preliminary phytochemical screening revealed the presence of flavonoids, alkaloids, carbohydrates & glycoside, saponins, and tannins. The methanol root extract had the highest activity in the DPPH assay, providing IC50 (50% inhibition) of 10.87µg/ml, followed by n-Hexane (IC50 74.10µg/ml) and chloroform (IC50 74.31µg/ml) extract. In the antibacterial assay, the chloroform extract was active against E. coli (24.00±0.15) and had moderate activity against Staph. aureus (12.5±0.18). The n-Hexane extract was completely inactive against the test organisms while the methanol extract showed poor activity against the test organisms. The present study adds to the existing literature on Cyphostemma adenocaule with scientific evidence into its biological properties.
ATP synthase subunit c (AtpE) is an enzyme that catalyzes the production of ATP from ADP in the presence of sodium or proton gradient from Mycobacterium tuberculosis (MTB). This enzyme considered an essential target for drug design and shares the same pathway with the target of Isoniazid. Thus, this enzyme would serve as an alternative target of the Isoniazid. The three dimensional (3D) model structure of the AtpE was constructed based on the principle of homology modeling using the Modeller9.16. The developed model was subjected to energy minimization and refinement using molecular dynamic (MD) simulation. The minimized model structure was searched against Zinc and PubChem database to determine ligands that bind to the enzyme with minimum binding energy using RASPD and PyRx tool. A total of 4776 compounds capable of bindings to AtpE with minimum binding energy were selected. These compounds further screened for physicochemical properties (Lipinski rule of five). All the compounds that possessed the desirable property selected and used for molecular docking analysis. Five (5) compounds with minimum binding energies ranged between ─8.69, and ─8.44 kcal/mol, less than the free binding energy of ATP were selected. These compounds further screened for the absorption, distribution, metabolism, excretion, and toxicity (ADME and toxicity) properties. Of the five compounds, three (ZINC14732869, ZINC14742188, and ZINC12205447) fitted all the ADME and toxicity properties and subjected to MD simulation and Molecular Mechanics Generalized Born and Surface Area (MM-GBSA) analyses. The results indicated that the ligands formed relatively stable complexes and had free binding energies, less than the binding energy of the ATP. Therefore, these ligands considered as prospective inhibitors of MTB after successful experimental validation.
The UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) catalyze the final steps of the UDP-N-acetylmuramic acid (UDPMurNAc) formation in the peptidoglycan biosynthesis pathway. The absence of this pathway in mammal made it an attractive target for drug development in Mycobacterium tuberculosis (MTB). In this study, the crystal structure of MurB from MTB (PDB Code: 5JZX and resolution of 2.2 Å) bound to FAD and K + was obtained from Protein Data Bank (PDB). A total of 2157 compounds with best binding conformations obtained from zinc database through virtual screening. These compounds further screened for drug-likeness, pharmacokinetic properties, physicochemical properties (Lipinski rule of five), and molecular docking analysis to obtained compounds with desirable therapeutic properties and good binding energies against MurB. Seven compounds (7) with minimum binding energies ranged between ─11.80 and ─10.39kcal/mol were selected, lower than the binding energy of FAD (─10.06kcal/mol). Four compounds with best binding energies (ZINC19837204 = ─11.80kcal/mol, ZINC11839554 = ─11.47kcal/mol, ZINC14976552 = ─10.77kcal/mol) and ability to interact with the residues (ZINC12242812 = ─10.39kcal/mol) of the substrate binding site further selected for the molecular dynamic (MD) simulation analysis. The result of the MD simulation showed that all the four ligands formed stable complexes in the binding site of the MurB, during the 50ns MD simulation, when compared with the cofactor (FAD). Therefore, these compounds were proposed to be novel inhibitors of MTB after in vivo and in vitro validation. File list (1) download file view on ChemRxiv MurB.docx (1.72 MiB) Molecular Docking and Dynamic Simulation of UDP-N-Acetylenolpyruvoylglucosamine Reductase (MurB) obtained from Mycobacterium tuberculosis using in silico Approach
The present work was conducted to isolate, screen and identify polyhydroxybutyrate (PHB)-producing bacteria from municipal wastes. Samples were collected from dumping sites of Maiduguri Borno State and were checked for their bacterial population using nutrient agar and PHB Detection agar (PDA). A total of 20 PHB-producing bacteria were isolated and identified. Of the total, four of the isolates were found to be from Paenibacillus spp. while the remaining 16 were Bacillus spp. Isolates from Ngomari Custin denoted as NC 5, 2; NC 7, and NC 5A were suspected to be Paenibacillus favisporus, Bacillus lentus, and Bacillus firmus respectively while others of NC 7A X, NC 6A and NC 7A Y of the same site were all found to be Bacillus smithii. Isolates from Old Maiduguri Graveyard denoted as OMG 5X, OMG 7, OMG 6 and OMG 5A were all found to be Bacillus smithii. The isolates from Flour Mill Area denoted as FMA 5A, FMA 6A, FMA Y, and FMA7B were found to be Bacillus smithii, Paenibacillus nanensis, Bacillus acidiceler and Paenibacillus septentrionalis respectively. On the other hand, isolates from Ramat Square site denoted as RS 6,2; RS 6A, RS 5, RS 7,2 were registered as Bacillus nealsonii, Paenibacillus cookie, Bacillus firmus and Bacillus megaterium respectively. Those of RS 5B and RS 7A of the same sample site were both Bacillus acidiceler and their granules were stained by Nile Blue A staining and observed under the fluorescence microscope and were classified for the extent of their PHB production based on the intensity of fluorescence emitted under the microscopy. NC 7 produced the highest PHB yield compared to all other isolates. Hence, municipal wastes are a rich reservoir of PHB-producing bacteria and can readily produce (PHB), which has enormous advantages over petroleum-based polymers by means of cost effectiveness and eco-friendliness
<p>The UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) catalyze the final steps of the UDP-N-acetylmuramic acid (UDPMurNAc) formation in the peptidoglycan biosynthesis pathway. The absence of this pathway in mammal made it an attractive target for drug development in <i>Mycobacterium tuberculosis</i> (MTB). In this study, the crystal structure of MurB from MTB (PDB Code: 5JZX and resolution of 2.2 Å) bound to FAD and K<sup>+</sup> was obtained from Protein Data Bank (PDB). A total of 2157 compounds with best binding conformations obtained from zinc database through virtual screening. These compounds further screened for drug-likeness, pharmacokinetic properties, physicochemical properties (Lipinski rule of five), and molecular docking analysis to obtained compounds with desirable therapeutic properties and good binding energies against MurB. Seven compounds (7) with minimum binding energies ranged between ─11.80 and ─10.39kcal/mol were selected, lower than the binding energy of FAD (─10.06kcal/mol). Four compounds with best binding energies (ZINC19837204 = ─11.80kcal/mol, ZINC11839554 = ─11.47kcal/mol, ZINC14976552 = ─10.77kcal/mol) and ability to interact with the residues (ZINC12242812 = ─10.39kcal/mol) of the substrate binding site further selected for the molecular dynamic (MD) simulation analysis. The result of the MD simulation showed that all the four ligands formed stable complexes in the binding site of the MurB, during the 50ns MD simulation, when compared with the cofactor (FAD). Therefore, these compounds were proposed to be novel inhibitors of MTB after <i>in vivo</i> and <i>in vitro</i> validation.</p>
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