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.

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 Densely Functionalized 2-methylideneazetidines: Evaluation as Antibacterials

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3891
Author(s):  
Giovanni Petrillo ◽  
Cinzia Tavani ◽  
Lara Bianchi ◽  
Alice Benzi ◽  
Maria Maddalena Cavalluzzi ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Inhibitory Concentration ◽  
General Procedure ◽  
Eukaryotic Cells ◽  
Gram Negative Bacteria ◽  
Pharmacological Profile ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Structure Activity

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common β-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria (E. faecalis and three strains of S. aureus), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(p-tolyl)azetidine 22, which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1–2 μg/mL, respectively). Since 22 combines a relatively efficient activity against Gram-positive bacteria and a cytotoxicity on eucharyotic cells only at 4-times higher concentrations (inhibiting concentration on 50% of the cultured eukaryotic cells: 36 ± 10 μM, MIC: 8.6 μM), it may be considered as a promising hit compound for the development of a new series of antibacterials selectively active on Gram-positive pathogens. The relatively concise synthetic route described herein, based on widely available starting materials, could feed further structure–activity relationship studies, thus allowing for the fine investigation and optimization of the toxico-pharmacological profile.

scholarly journals Synthesis and Antibacterial Activity of Novel Schiff Bases of Thiosemicarbazone Derivatives With Adamantane Moiety

2021 ◽  
Author(s):  
Jiahui Zhu ◽  
Guosheng Teng ◽  
Dongfeng Li ◽  
Ruibin Hou ◽  
Yan Xia
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Inhibitory Effect ◽  
Negative Bacterium ◽  
Gram Negative ◽  
Major Threat ◽  
Antibiotic Drugs

Abstract Increased bacterial resistance to antibiotics is a major threat to human health, and it is particularly important to develop novel antibiotic drugs. Here, we designed a series of Schiff base thiosemicarbazone derivatives containing an adamantane moiety, and carried out structural characterization of the compounds and in vitro antibacterial activity tests. Compound 7e was as effective as the commonly-used antibiotic ampicillin against the Gram-negative bacterium Escherichia coli, and compound 7g had a good inhibitory effect against Gram-positive Bacillus subtilis. These findings provide data for the development of better thiosemicarbazone antibacterial agents.

scholarly journals АNTIBACTERIAL THERAPY IN PATIENTS WITH PNEUMOEMPYEMA

2021 ◽  
pp. 102-105
Author(s):  
D. Lopatenko ◽  
M. Sykal ◽  
A. Syvozhelizov ◽  
O. Tonkoglas ◽  
V. Kolesnik
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Therapy ◽  
Staphylococcus Epidermidis ◽  
Antibacterial Agents ◽  
Antifungal Agents ◽  
Pleural Cavity ◽  
Generation Cephalosporin ◽  
Initial Therapy ◽  
Gram Negative ◽  
Gram Positive Bacteria

Summary. Purpose of the work. To study the structure of the pathogenic flora in pneumoempyema and its sensitivity to antibacterial agents. Materials and methods. It were examined 159 patients of both sexes, with pneumoempyema. We detected the species of microflora, and its sensitivity to antibacterial agents. The material for bacteriological studies was pleural exudates, wich we obtained from the pleural cavity by the puncture method. Research results. The characteristic of the pleurals flora has been revealed, the sensitivity of these pathogens to antibacterial drugs has also been detected. We have made antibacterial therapy schemes for patients with pneumoempyema. Conclusions. In the etiology of pneumoempyema predominate next gram-positive bacteria: Streptococcus pneumoniae, Staphylococcus epidermidis, Staphylococcus aureus, which were sensitive to inhibitor-protected penicillins, and 4th generation cephalosporins. Gram-negative flora was represented by Pseudomonada aerugenosa, Escherichia Coli, Enterobacter spp., which were sensitive to fluorchinolones of III and IV generations and carbapenems. We have proposed schemes of antibacterial therapy: A. Initial therapy: 4th generation cephalosporin + 3th–4th generation fluoroquinolone. B. Reserve scheme: inhibitor-protected penicillin + carbapenems. These combinations are most effective against 96.0 % of microorganisms identified by us. In case of prescribing two or more antibacterial agents, as well as with antibacterial therapy for seven days or more, antifungal agents should be prescribed.

scholarly journals Sintesis dan Uji Aktivitas Antibakteri Senyawa N-fenil-4-klorobenzamida

2018 ◽  
Vol 6 (2) ◽  
pp. 212
Author(s):  
Elok Dea Orens Ubung Wisnu ◽  
Indah Purnama Sary ◽  
Dwi Koko Pratoko
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Antibacterial Agent ◽  
Diffusion Method ◽  
Gram Negative Bacteria ◽  
Crystal Shape ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Benzamide Derivatives

N-phenylbenzamide is benzamide derivatives, which is potential as an antibacterial agent. N-phenyl-4-chlorobenzamide is N-phenylbenzamide derivative that substitued by chloro to the para position and it was expected to enhance the antibacterial activity. N-phenyl-4-chlorobenzamide was synthesized by reacting 1,3-diphenyilthiourea and 4-chlorobenzoil chloride. This compound has been purified and provided 53% of product with crystal shape, white color, and melting point of 195-197 oC. The purification of this compound was confirmed by TLC and the structure was identified by 1H-NMR, 13C-NMR, and FTIR spectroscopy. This compound was tested for its activity against gram positive bacteria Staphylococcus aureus and gram negative bacteria Pseudomonas aeruginosa, evaluated by well diffusion method and the result showed no activity against both Staphylococcus aureus and Pseudomonas aeruginosa.   Keywords: N-phenyl-4-chlorobenzamide, synthesis, antibacterial activity

scholarly journals Antimicrobial Peptide Resistance Genes in the Plant Pathogen Dickeya dadantii

2016 ◽  
Vol 82 (21) ◽  
pp. 6423-6430 ◽  
Author(s):  
Caroline Pandin ◽  
Martine Caroff ◽  
Guy Condemine
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Soft Rot ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Dickeya Dadantii ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
New Genes

ABSTRACTModification of teichoic acid through the incorporation ofd-alanine confers resistance in Gram-positive bacteria to antimicrobial peptides (AMPs). This process involves the products of thedltXABCDgenes. These genes are widespread in Gram-positive bacteria, and they are also found in a few Gram-negative bacteria. Notably, these genes are present in all soft-rot enterobacteria (PectobacteriumandDickeya) whosedltDXBACoperons have been sequenced. We studied the function and regulation of these genes inDickeya dadantii.dltBexpression was induced in the presence of the AMP polymyxin. It was not regulated by PhoP, which controls the expression of some genes involved in AMP resistance, but was regulated by ArcA, which has been identified as an activator of genes involved in AMP resistance. However,arcAwas not the regulator responsible for polymyxin induction of these genes in this bacterium, which underlines the complexity of the mechanisms controlling AMP resistance inD. dadantii. Two other genes involved in resistance to AMPs have also been characterized,phoSandphoH.dltB,phoS,phoH, andarcAbut notdltDmutants were more sensitive to polymyxin than the wild-type strain. Decreased fitness of thedltB,phoS, andphoHmutants in chicory leaves indicates that their products are important for resistance to plant AMPs.IMPORTANCEGram-negative bacteria can modify their lipopolysaccharides (LPSs) to resist antimicrobial peptides (AMPs). Soft-rot enterobacteria (DickeyaandPectobacteriumspp.) possess homologues of thedltgenes in their genomes which, in Gram-positive bacteria, are involved in resistance to AMPs. In this study, we show that these genes confer resistance to AMPs, probably by modifying LPSs, and that they are required for the fitness of the bacteria during plant infection. Two other new genes involved in resistance were also analyzed. These results show that bacterial resistance to AMPs can occur in bacteria through many different mechanisms that need to be characterized.

scholarly journals A phytomass-inspired carbon and its importance as an antibacterial agent against human pathogens

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
N. Anvarsha ◽  
P. Kalyani
Keyword(s):  
Activated Carbon ◽  
Elemental Analysis ◽  
Antibacterial Agent ◽  
Low Cost ◽  
Diffusion Method ◽  
Vitex Negundo ◽  
Human Pathogens ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

Abstract Background Imprudent use of antimicrobial drugs has resulted in the microbial resistance among the known microbes and hence we foresee a pressing need towards the development of novel, low-cost, and high potent antimicrobials which should be munificent by nature. In the pursuit of the above, phosphoric acid activated low-cost carbon was produced from a renewable phytomass precursor viz., leaves of Vitex negundo L. plant and explored for its antibacterial efficacy against four human pathogens viz., S. aureus, S. pyogenes (Gram-positive bacteria), and E. coli, P. aeruginosa (Gram-negative bacteria) by adopting well diffusion method. Carbon yield, burn-off, phase purity, elemental composition, particle morphology, and surface functionalities have been studied by ultimate elemental analysis, X-ray diffractometry, elemental analysis, scanning electron microscopy, and Fourier transform infrared spectrophotometry respectively. Minimal inhibition concentration (MIC) was also followed. Plausible mechanism of killing the pathogens by the above activated carbon was also provided. Results Vitex negundo leaves derived activated carbon (VNLAC) was found to contain large number of O-, S- and N-containing surface groups which are supposedly responsible for bestowing antibacterial properties to the carbon derived from Vitex negundo leaves. It has emerged as a potential antibacterial agent for many Gram-negative as well as Gram-positive bacteria. The inhibition zone of mean diameters ranged from 9 to 25 mm against all the pathogens was significantly (p < 0.05) less than that of the control viz., ciprofloxacin. Thus, the fundamental experimental results may extend the limits of carbon sources but also the conventional idea of obtaining active carbon to apply in technologies where carbon is inevitable. Conclusion The work not only demonstrates the promising potential of VNLAC as an efficient antibacterial agent but also presents a feasible mechanism of action of removing pathogens. Vitex negundo-derived carbon may become a cheap substitute for cost-prohibitive drugs. The findings of the work illustrate an easy choice as an antibacterial for topical application at infected sites.

Bacterial Communications in Implant Infections: A Target for an Intelligence War

2007 ◽  
Vol 30 (9) ◽  
pp. 757-763 ◽  
Author(s):  
J.W. Costerton ◽  
L. Montanaro ◽  
C.r. Arciola
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Homoserine Lactone ◽  
Bacterial Virulence ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Sensing Systems

The status of population density is communicated among bacteria by specific secreted molecules, called pheromones or autoinducers, and the control mechanism is called “quorum-sensing”. Quorum-sensing systems regulate the expression of a panel of genes, allowing bacteria to adapt to modified environmental conditions at a high density of population. The two known different quorum systems are described as the LuxR-LuxI system in gram-negative bacteria, which uses an N-acyl-homoserine lactone (AHL) as signal, and the agr system in gram-positive bacteria, which uses a peptide-tiolactone as signal and the RNAIII as effector molecules. Both in gram-negative and in gram-positive bacteria, quorum-sensing systems regulate the expression of adhesion mechanisms (biofilm and adhesins) and virulence factors (toxins and exoenzymes) depending on population cell density. In gram-negative Pseudomonas aeruginosa, analogs of signaling molecules such as furanone analogs, are effective in attenuating bacterial virulence and controlling bacterial infections. In gram-positive Staphylococcus aureus, the quorum-sensing RNAIII-inhibiting peptide (RIP), tested in vitro and in animal infection models, has been proved to inhibit virulence and prevent infections. Attenuation of bacterial virulence by quorum-sensing inhibitors, rather than by bactericidal or bacteriostatic drugs, is a highly attractive concept because these antibacterial agents are less likely to induce the development of bacterial resistance.

scholarly journals Structure-Antibacterial Activity Relationships Of N-Substituted-(D-/L-Alaninyl) 1H-1,2,3-Triazolylmethyl Oxazolidinones

2018 ◽  
Author(s):  
Oludotun Phillips ◽  
Edet Ekpenyong Udo ◽  
Roselyn Jennifer D’silva
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Clinical Usefulness ◽  
Antibacterial Resistance ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Resistance Development ◽  
Antibacterial Drugs ◽  
Gram Negative

Bacterial resistance towards existing class of antibacterial drugs continues to increase posing significant threat to clinical usefulness of these drugs. This increasing and alarming rates of antibacterial resistance development and the decline in the number of new antibacterial drugs approval continue to serve as major impetus for research into discovery and development of new antibacterial agents. We synthesized a series D-/L-alaninyl substituted triazolyl oxazolidinone derivatives and evaluated their antibacterial activity against selected standard Gram-positive and Gram-negative bacterial strains. Overall, the compounds showed moderate to strong antibacterial activity. Compounds 9d and 10d (D- and L-alaninyl derivatives bearing 3,5-dinitrobenzoyl substituent), 10e (D-alaninyl derivative bearing 5-nitrofurancarbonyl group) and 9f and 10f (D- and L-alaninyl derivatives bearing 5-nitrothiophene carbonyl moiety) demonstrated antibacterial activity (MIC:2 g/mL) against S. aureus, S. epidermidis, E. faecalis and M. catarrhalis standard bacterial strains. No significant differences were noticeable between the antibacterial activity of the D- and L-alaninyl derivatives as a result of the stereochemistry of the compounds.

scholarly journals Synthesis of Novel Antibacterial Agents: 1-(2', 4'-Dihydroxy-5'-chlorophenyl)-3-arylpropane-1, 3-Diones

2009 ◽  
Vol 6 (3) ◽  
pp. 705-712 ◽  
Author(s):  
J. I. Sheikh ◽  
V. N. Ingle ◽  
H. D. Juneja
Keyword(s):  
Convenient Method ◽  
Antibacterial Agents ◽  
Antibacterial Efficacy ◽  
Gram Positive ◽  
Spectral Analyses ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
C Nmr

1-(2', 4'-Dihydroxy-5'-chlorophenyl)-3-arylpropane-1, 3-diones(3a-h) have been synthesized by a simple and convenient method employing Baker-Venkatraman transformation on 2-aroyloxy-4-hydroxy-5-chloroacetophenones (2a-h) with NaOH in dimethylsuphoxide regardless of pyridine. The structures of the synthesized compounds have been assigned on the basis of elemental and spectral analyses (IR,1HNMR,13C NMR, Mass). The synthesized compounds were evaluated for the antibacterial efficacy against gram negative and gram positive bacteria.

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