scholarly journals Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 386
Author(s):  
Emilio Lamazares ◽  
Desmond MacLeod-Carey ◽  
Fernando P. Miranda ◽  
Karel Mena-Ulecia
Keyword(s):  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Antihypertensive Agents ◽  
Dynamics Simulation ◽  
Ligand Efficiency ◽  
Promising Candidate ◽  
Theoretical Evaluation ◽  
Gram Positive Bacteria ◽  
Poisson Boltzmann

The search for new antibacterial agents that could decrease bacterial resistance is a subject in continuous development. Gram-negative and Gram-positive bacteria possess a group of metalloproteins belonging to the MEROPS peptidase (M4) family, which is the main virulence factor of these bacteria. In this work, we used the previous results of a computational biochemistry protocol of a series of ligands designed in silico using thermolysin as a model for the search of antihypertensive agents. Here, thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family, was used to determine the most promising candidate as an antibacterial agent. Our results from docking, molecular dynamics simulation, molecular mechanics Poisson–Boltzmann (MM-PBSA) method, ligand efficiency, and ADME-Tox properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) indicate that the designed ligands were adequately oriented in the thermolysin active site. The Lig783, Lig2177, and Lig3444 compounds showed the best dynamic behavior; however, from the ADME-Tox calculated properties, Lig783 was selected as the unique antibacterial agent candidate amongst the designed ligands.

scholarly journals Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus Thermoproteolyticus as Possible Antibacterial Agents

2020 ◽  
Author(s):  
Emilio Lamazares ◽  
Desmond MacLeod-Carey ◽  
Fernando P. Miranda ◽  
Karel Mena-Ulecia
Keyword(s):  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Comprehensive Analysis ◽  
Dynamics Simulation ◽  
Ligand Efficiency ◽  
Theoretical Evaluation ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Computational Protocol

The search for new antibacterial agents that could decrease bacterial resistance is a subject that is continuously developing. The Gram-negative and Gram-positive bacteria have a metalloproteins group belonging to the M4 family. That is the main virulence factor of these bacteria. In this work, we have used a computational protocol based on the comprehensive analysis of the results of docking, molecular dynamics simulation, MM-PBSA, ligand efficiency, and ADME-Tox properties of ligand designed in silico in the previous manuscript using the Thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family as a target. The principal results obtained were the designed ligands were adequately oriented in the thermolysin active center. The Lig783, Lig2177, and Lig3444 compounds were those with better dynamic behavior, however, when analyzing the results extracted from the ADME-Tox properties, only Lig783 was the best antibacterial agent candidate.

A REVIEW ON NATURAL ANTI BIOFILM AGENTS FOR WOUND BIOFILM

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (10) ◽  
pp. 7-18
Author(s):  
Mahipriyaa S. R. ◽  
Baby Roselin R ◽  
Arjun K. ◽  
Nithyanth M. ◽  
Sankar V. ◽  
...  
Keyword(s):  
Natural Products ◽  
Growth And Development ◽  
Antibacterial Agents ◽  
Extracellular Polymeric Substances ◽  
Bacterial Resistance ◽  
Bacterial Biofilms ◽  
Wound Infections ◽  
Promising Candidate ◽  
Biofilm Growth ◽  
Micro Organisms

A biofilm may be a consortium of micro-organisms in which the cells of microbes attach to each other on a living or non-living surface inside a self-produced matrix of extracellular polymeric substances. The bacterial or fungal colonies invade the surface of the wounds, thereby delaying the healing cascade. The resistance is partially due to low metabolic rate of these colonies, which directly impacts the action of oral or parenteral antibiotics. Hence, there is an urgent need to develop antibacterial agents to regulate the biofilm growth and development. The last few decades have witnessed wide research studies attempting to investigate the anti-biofilm effects of natural products. This review will summarize the wound infections associated with biofilm, mechanisms of bacterial resistance due to biofilm and recent studies on discovery of natural products with their mechanisms for inhibiting various bacterial biofilms that can be a promising candidate which could provide novel strategies for biofilm-associated infections.

Structure prediction of SPAK C-terminal domain and analysis of its binding to RFXV/I motifs by homology modelling, docking, and molecular dynamics simulation studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Mubarak A. Alamri ◽  
Ahmed D. Alafnan ◽  
Obaid Afzal ◽  
Alhumaidi B. Alabbas ◽  
Safar M. Alqahtani
Keyword(s):  
Molecular Dynamic ◽  
Dynamic Stability ◽  
Md Simulation ◽  
Homology Modelling ◽  
Antihypertensive Agents ◽  
Structure And Function ◽  
Dynamics Simulation ◽  
Dimensional Structure ◽  
Terminal Domain ◽  
And Function

Background: The STE20/SPS1-related proline/alanine-rich kinase (SPAK) is a component of WNKSPAK/OSR1 signaling pathway that plays an essential role in blood pressure regulation. The function of SPAK is mediated by its highly conserved C-terminal domain (CTD) that interacts with RFXV/I motifs of upstream activators, WNK kinases, and downstream substrate, cation-chloride cotransporters. Objective: To determine and validate the three-dimensional structure of the CTD of SPAK and to study and analyze its interaction with the RFXV/I motifs. Methods: A homology model of SPAK CTD was generated and validated through multiple approaches. The model was based on utilizing the OSR1 protein kinase as a template. This model was subjected to 100 ns molecular dynamic (MD) simulation to evaluate its dynamic stability. The final equilibrated model was used to dock the RFQV-peptide derived from WNK4 into the primary pocket that was determined based on the homology sequence between human SPAK and OSR1 CTDs. The mechanism of interaction, conformational rearrangement and dynamic stability of the binding of RFQV-peptide to SPAK CTD were characterized by molecular docking and molecular dynamic simulation. Results: The MD simulation suggested that the binding of RFQV induces a large conformational change due to the distribution of salt bridge within the loop regions. These results may help in understanding the relation between the structure and function of SPAK CTD and to support drug design of potential SPAK kinase inhibitors as antihypertensive agents. Conclusion: This study provides deep insight into SPAK CTD structure and function relationship.

scholarly journals Silver Nanoparticles and Their Antibacterial Applications

2021 ◽  
Vol 22 (13) ◽  
pp. 7202
Author(s):  
Tamara Bruna ◽  
Francisca Maldonado-Bravo ◽  
Paul Jara ◽  
Nelson Caro
Keyword(s):  
Silver Nanoparticles ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Secondary Effects ◽  
Cytotoxic Effects ◽  
Factors Affecting ◽  
Gram Positive Bacteria ◽  
Resistant Strains

Silver nanoparticles (AgNPs) have been imposed as an excellent antimicrobial agent being able to combat bacteria in vitro and in vivo causing infections. The antibacterial capacity of AgNPs covers Gram-negative and Gram-positive bacteria, including multidrug resistant strains. AgNPs exhibit multiple and simultaneous mechanisms of action and in combination with antibacterial agents as organic compounds or antibiotics it has shown synergistic effect against pathogens bacteria such as Escherichia coli and Staphylococcus aureus. The characteristics of silver nanoparticles make them suitable for their application in medical and healthcare products where they may treat infections or prevent them efficiently. With the urgent need for new efficient antibacterial agents, this review aims to establish factors affecting antibacterial and cytotoxic effects of silver nanoparticles, as well as to expose the advantages of using AgNPs as new antibacterial agents in combination with antibiotic, which will reduce the dosage needed and prevent secondary effects associated to both.

An AIEgen as an Intrinsic Antibacterial Agent for Light‐Up Detection and Inactivation of Intracellular Gram‐Positive Bacteria

2021 ◽  
pp. 2100885
Author(s):  
Tianjiao Dai ◽  
Bingpeng Guo ◽  
Guobin Qi ◽  
Shidang Xu ◽  
Cheng Zhou ◽  
...  
Keyword(s):  
Antibacterial Agent ◽  
Gram Positive ◽  
Gram Positive Bacteria

Study on the Antibacterial Performance of the Antibacterial Shutter Blades

2013 ◽  
Vol 815 ◽  
pp. 333-338
Author(s):  
Ming Li Liu ◽  
Chun Feng Li ◽  
Yun Long Wang ◽  
Kai Lu ◽  
Jiu Yin Pang ◽  
...  
Keyword(s):  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
Drug Loading ◽  
Antibacterial Properties ◽  
Water Soluble ◽  
Single Factor ◽  
Antibacterial Performance ◽  
Loading Amount ◽  
Single Factor Experiment ◽  
Impregnation Solution

This study used Ag-embedded nanoTiO2, xylan and water-soluble Chitosan as antibacterial agents, respectively prepared shutter blades through the treating solution of the different concentration and the different drug loading amount of the poplar veneer. Through a single factor experiment, this paper analyzes that the different antibacterial agent, concentration of antibacterial agent and the drug loading amount have an effect on the antibacterial properties of the shutter blades. The results show that the order of antibacterial performance of the shutter blades impregnated antibacterial agents is the Ag-embedded nanoTiO2, Chitosan, Xylan. Comprehensiv-ely thought the antibacterial properties and economic index, the optimal concentration of the Ag-embedded nanoTiO2 impregnation solution is 1%.

scholarly journals In Silico Potential of Turmeric (Cucurma longa) as Antibacterial Agent for Salmonella typhi

BIOEDUKASI ◽  
2018 ◽  
pp. 103
Author(s):  
Boni Herdiawan ◽  
Dwi Rulitasari ◽  
Ella Triana Aprilianty ◽  
Huzaimatul Khalisah ◽  
Nur Fatichah Choirudiniyah ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
In Silico ◽  
Antibacterial Agent ◽  
Bacterial Resistance ◽  
Curcuma Longa ◽  
Salmonella Typhi ◽  
Amino Acid Residues ◽  
Tropical Country ◽  
Receptor Proteins ◽  
Docking Method

Indonesia is a tropical country that has a variety of endemic infectious diseases, one of these diseases is typhoid fever. Salmonella typhi is a bacterium that causes typhoid fever. Antibiotic treatment is often used but fails due to bacterial resistance to antibiotics. An alternative treatment is required to gradually substitute synthetic antibiotic. One of this potential is given by turmeric (Curcuma longa).The purpose of this research was to know the potential of turmeric as in silico antibacterial agent for Salmonella typhi using docking method. Docking result showed that the five compounds produced different values ​​on the affinity and rmsd binding parameters. The highest affinity binding value was the Ciprofloxacin compound, the lowest was Bisdemethoxycurcumin compound. The highest rmsd value was Demethoxycurcumin, while the lowest was Xanthorrhizol, and the result revealed that all compounds have bioaffinity properties. Based on the results, three compounds derived from turmeric (demethoxycurcumin, bisdemethoxy curcumin and xanthorrizol) are still not effectively used as antibacterial agent for Salmonella typhi due to the absence of equality of amino acid residues between alternative compounds turmeric with compounds which has been clinically tested as a drug and ineffective use of receptor proteins that result in less optimal alternative compounds.   Keywords: Turmeric, Antibacterial, Salmonella typhi, In Silico

Antibiotic adjuvants: a promising approach to combat multidrug resistant bacteria

2021 ◽  
Vol 22 ◽  
Author(s):  
Namita Sharma ◽  
Anil K. Chhillar ◽  
Sweety Dahiya ◽  
Pooja Choudhary ◽  
Aruna Punia ◽  
...  
Keyword(s):  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibacterial Drugs ◽  
Effective Strategies ◽  
The Impact ◽  
Emergence Of Resistance

The escalating emergence and prevalence of infections caused by multi-drug resistant (MDR) pathogenic bacteria accentuate the crucial need to develop novel and effectual therapeutic strategies to control this threat. Recent past surprisingly indicates a staggering decline in effective strategies against MDR. Different approaches have been employed to minimize the effect of resistance but the question still lingers over the astounding number of drugs already tried and tested to no avail, furthermore, the detection of new drug targets and the action of new antibacterial agents against already existing drug targets also complicate the condition. Antibiotic adjuvants are considered as one such promising approach for overcoming the bacterial resistance. Adjuvants can potentiate the action of generally adopted antibacterial drugs against MDR bacterial pathogens either by minimizing the impact and emergence of resistance or improving the action of antibacterial drugs. This review provides an overview of mechanism of antibiotic resistance, main types of adjuvants and their mode of action, achievements and progression.

Antimicrobial Applications of Nanoparticles

2022 ◽  
pp. 269-288
Author(s):  
Ayesha Kanwal ◽  
Zeeshan Ahmad Bhutta ◽  
Ambreen Ashar ◽  
Ashar Mahfooz ◽  
Rizwan Ahmed ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Side Effects ◽  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
The Other ◽  
Drug Resistant ◽  
Short Term ◽  
Human Mortality ◽  
Recent Developments

Human mortality due to drug-resistant infections is becoming more prevalent in our society. Antibiotics are impotent due to abuse and/or misuse, leading to new, more expensive, and more effective medicines and treatments. Therefore, it causes many short-term and long-term side effects in the patient. On the other hand, nanoparticles have exhibited antibacterial activity against various pathogens due to their small size and ability to destroy cells by various mechanisms. Unlike antibiotics for the treatment of patients' diseases and infections, nanomaterials provide an exciting way to limit the growth of microorganisms due to infections in humans. This has led to the development of a number of nanoparticles as active antibacterial agents. Therefore, the authors have carefully reviewed the recent developments in the use of nanomaterials for antibacterial applications and the mechanisms that make them an effective alternate antibacterial agent.

scholarly journals NB2001, a Novel Antibacterial Agent with Broad-Spectrum Activity and Enhanced Potency against β-Lactamase-Producing Strains

2002 ◽  
Vol 46 (5) ◽  
pp. 1262-1268 ◽  
Author(s):  
Qing Li ◽  
Jean Y. Lee ◽  
Rosario Castillo ◽  
Mark S. Hixon ◽  
Catherine Pujol ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antibacterial Agent ◽  
Bacterial Resistance ◽  
Enterobacter Aerogenes ◽  
Order Rate Constant ◽  
Common Mechanism ◽  
E Coli ◽  
Lactam Ring ◽  
Spectrum Activity ◽  
Hydrolysis Of

ABSTRACT Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to overcome drug resistance resulting from enzyme overexpression. β-Lactamase overexpression is a common mechanism of bacterial resistance to β-lactam antibiotics. We present here the results for one of the β-lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold. Unlike conventional β-lactam antibiotics, where hydrolysis of the β-lactam ring inactivates the antibiotic, hydrolysis of NB2001 by β-lactamase releases triclosan. Evidence supporting the proposed mechanism is as follows. (i) NB2001 is a substrate for TEM-1 β-lactamase, forming triclosan with a second-order rate constant (k cat/Km ) of greater than 77,000 M−1 s−1. (ii) Triclosan is detected in NB2001-treated, β-lactamase-producing Escherichia coli but not in E. coli that does not express β-lactamase. (iii) NB2001 activity against β-lactamase-producing E. coli is decreased in the presence of the β-lactamase inhibitor clavulanic acid. NB2001 was similar to or more potent than reference antibiotics against clinical isolates of Staphylococcus aureus (including MRSA), Staphylococcus epidermidis, Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Moraxella catarrhalis and Haemophilus influenzae. NB2001 is also active against Klebsiella pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. The results indicate that NB2001 is a potent, broad-spectrum antibacterial agent and demonstrate the potential of ECTA in overcoming β-lactamase-mediated resistance.

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