scholarly journals In Silico Toxicological, Anti-Tubercular Effect Evaluation And In Vitro Marine Pathogenic Bacteria Inhibition of N-[(3-Chloro-4-Nitro-Phenyl)Methyleneamino]Pyridine-4-Carboxamidine

2019 ◽  
Vol 9 (6) ◽  
pp. 23-27
Author(s):  
Kamel Mokhnache ◽  
EL-Khamsa Soltani ◽  
Soraya Madoui ◽  
Hanane Khither ◽  
Ahlem Karbab ◽  
...  
Keyword(s):  
In Silico ◽  
Pathogenic Bacteria ◽  
Vibrio Anguillarum ◽  
Subcutaneous Administration ◽  
Covalent Bond ◽  
Metabolic Activation ◽  
Bactericidal Effect ◽  
Effect Evaluation ◽  
Photobacterium Damselae

The hydrazone; N-[(3-chloro-4-nitro-phenyl) methyleneamino] pyridine-4-carboxamidine (H) was selected for in silico toxicological and in vitro bactericidal studies. Toxicological investigation was carried out using software program, such as eMolTox and Gusar, for the toxic substructure determination, and acute rat toxicity prediction respectively. In vitro bactericidal effect evaluation was investigated using tow marine pathogenic bacteria; Vibrio anguillarum and Photobacterium damselae. Computational results determinate toxicophores of (H), which are nitro-aromatic part, hydrazine group, and quaternary carbon, were predicted as responsible for Idiosyncratic toxicity metabolic activation, covalent bond with DNA, and hepatotoxicity respectively. In addition, the predicted LD50 of (H) are 1086, 244, 1816, and 823.40 mg/kg in intraperitenial, intravenous, oral and subcutaneous administration respectively. For bactericidal results, H exhibited an excellent effect with inhibition percentages of 98.65 and 98.83% at the concentrations of 1000 and 500 µg/mL against Vibrio anguillarum respectively, the same effect was demonstrated against Photobacterium damselae with inhibition percentages of 97.74 and 97.98 % at the same concentrations. For anti-tubercular effect prediction, results revealed that H has an excellent effect with probability percentage of 84.6%.   Keyword: Hydrazone, toxicophore, LD50, Anti-tubercular, Vibrio anguillarum, Photobacterium damselae.     

Oxasetin from Lophiostoma sp. of the Baltic Sea: Identification, in silico Binding Mode Prediction and Antibacterial Evaluation against Fish Pathogenic Bacteria

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Muftah Ali M. Shushni ◽  
Faizul Azam ◽  
Ulrike Lindequist
Keyword(s):  
Baltic Sea ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Vibrio Anguillarum ◽  
Binding Mode ◽  
Docking Studies ◽  
The Baltic Sea ◽  
Minimal Inhibitory Concentrations ◽  
The Baltic

Because of the evolving resistance of microorganisms against existing antibiotics, there is an increasing need for new ones, not only in human, but also in veterinary medicine. The dichloromethane extract of a fungal strain of the genus Lophiostoma, isolated from driftwood collected from the coast of the Baltic Sea, displayed antibacterial activity against some fish pathogenic bacteria. Ergosterol epoxide (1), cerebroside C (2) and oxasetin (3) were isolated from the extract and structurally elucidated on the basis of spectroscopic data and chemical evidence. Compound 3 exhibited in vitro activity against Vibrio anguillarum, Flexibacter maritimus and Pseudomonas anguilliseptica with minimal inhibitory concentrations of 12.5, 12.5 and 6.25 μg/mL, respectively. Molecular docking studies were performed to understand the interaction of compound 3 with different macromolecular targets. Analysis of in silico results, together with experimental findings, validates the antimicrobial activity associated with compound 3. These results may be exploited in lead optimization and development of potent antibacterial agents.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

scholarly journals Antibacterial Activities and Molecular Docking of Novel Sulfone Biscompound Containing Bioactive 1,2,3-Triazole Moiety

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4817
Author(s):  
Huda R. M. Rashdan ◽  
Ihsan A. Shehadi ◽  
Mohamad T. Abdelrahman ◽  
Bahaa A. Hemdan
Keyword(s):  
Molecular Docking ◽  
Pathogenic Bacteria ◽  
Analytical Data ◽  
Docking Study ◽  
Antibacterial Activities ◽  
Bactericidal Effect ◽  
Bacterial Strains ◽  
Molecular Docking Study ◽  
Synthetic Compound

In this study, a new synthetic 1,2,3-triazole-containing disulfone compound was derived from dapsone. Its chemical structure was confirmed using microchemical and analytical data, and it was tested for its in vitro antibacterial potential. Six different pathogenic bacteria were selected. MICs values and ATP levels were determined. Further, toxicity performance was measured using MicroTox Analyzer. In addition, a molecular docking study was performed against two vital enzymes: DNA gyrase and Dihydropteroate synthase. The results of antibacterial abilities showed that the studied synthetic compound had a strong bactericidal effect against all tested bacterial strains, as Gram-negative species were more susceptible to the compound than Gram-positive species. Toxicity results showed that the compound is biocompatible and safe without toxic impact. The molecular docking of the compound showed interactions within the pocket of two enzymes, which are able to stabilize the compound and reveal its antimicrobial activity. Hence, from these results, this study recommends that the established compound could be an outstanding candidate for fighting a broad spectrum of pathogenic bacterial strains, and it might therefore be used for biomedical and pharmaceutical applications.

scholarly journals In Silico and In Vitro Evaluation of the Antimicrobial Potential of Bacillus cereus Isolated from Apis dorsata Gut against Neisseria gonorrhoeae

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1401
Author(s):  
Nurdjannah Jane Niode ◽  
Aryani Adji ◽  
Jimmy Rimbing ◽  
Max Tulung ◽  
Mohammed Alorabi ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Bacillus Cereus ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Hydrophobic Interactions ◽  
Binding Free Energy ◽  
Dynamics Simulation ◽  
Apis Dorsata ◽  
Associated Bacteria

Antimicrobial resistance is a major public health and development concern on a global scale. The increasing resistance of the pathogenic bacteria Neisseria gonorrhoeae to antibiotics necessitates efforts to identify potential alternative antibiotics from nature, including insects, which are already recognized as a source of natural antibiotics by the scientific community. This study aimed to determine the potential of components of gut-associated bacteria isolated from Apis dorsata, an Asian giant honeybee, as an antibacterial against N. gonorrhoeae by in vitro and in silico methods as an initial process in the stage of new drug discovery. The identified gut-associated bacteria of A. dorsata included Acinetobacter indicus and Bacillus cereus with 100% identity to referenced bacteria from GenBank. Cell-free culture supernatants (CFCS) of B. cereus had a very strong antibacterial activity against N. gonorrhoeae in an in vitro antibacterial testing. Meanwhile, molecular docking revealed that antimicrobial lipopeptides from B. cereus (surfactin, fengycin, and iturin A) had a comparable value of binding-free energy (BFE) with the target protein receptor for N. gonorrhoeae, namely penicillin-binding protein (PBP) 1 and PBP2 when compared with the ceftriaxone, cefixime, and doxycycline. The molecular dynamics simulation (MDS) study revealed that the surfactin remains stable at the active site of PBP2 despite the alteration of the H-bond and hydrophobic interactions. According to this finding, surfactin has the greatest antibacterial potential against PBP2 of N. gonorrhoeae.

scholarly journals 91 Electronic probes for assessment of changes in gastrointestinal microbiome in nursery pigs

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 25-26
Author(s):  
Scott D Carter ◽  
Kitty Cardwell ◽  
Andres Espindola Camacho ◽  
Ishtar Silva Lara
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Mitigation Strategies ◽  
Commensal Bacteria ◽  
Metagenomic Sequencing ◽  
Metagenomic Sequence ◽  
Nursery Pigs

Abstract Gut microbiota play an important role in extraction, synthesis and absorption of nutrients. Commensal bacteria prevent pathogenic bacteria colonization and maintain intestinal epithelium integrity. The most common families of commensal bacteria in nursery pigs are Prevotellaceae, Clostridiaceae, Erysipelotrichaceae, Lachnospitaceae, Lactobacillaceae, Ruminicoccaceae and Streptoccocaceae. Understanding the microbial abundance shifts that causes health disruption leading to diarrhea and stunted growth performance can be of great benefit for developing mitigation strategies. Next generation sequencing (NGS) technology facilitates metagenomic approaches, developing sequencing profile representing any and all organisms within a sample. Electronic-probe Diagnostic Nucleic acid Analysis (EDNA) is a bioinformatic tool originally developed to detect species-specific plant pathogen targets in metagenomic databases. EDNA has been shown to reduce time to detect microbial signatures in large metagenomic sequence data. However, it has not previously been used as a metagenomic tool for assessing microbiome composition at the family level. Therefore, a metagenomic sequencing based in silico detection of gut microbiota using E-probes of the seven most common commensal families was developed and further validated in vitro. E-probes were designed from the selected families as follows, Prevotellaceae (89,565), Clostridiaceae (58,554), Erysipelotrichaceae (195), Lachnospitaceae (87), Lactobacillaceae (211,507), Ruminicoccaceae (14,575) and Streptoccocaceae (54,632). Fecal metagenomes of nursery pigs from 0, 7, 14, and 21 d were used to validate the E-probes. The hits were able to detect the relative abundance variations of the 4-time periods. The results between hits and reads were as follows, Prevotellaceae (r2 = 0.98), Clostridiaceae (r2 = 0.99), Erysipelotrichaceae (r2 = 0.99), Lachnospitaceae (r2 = 0.99), Lactobacillaceae (r2 = 0.91), Ruminicoccaceae (r2 = 0.99) and Streptoccocaceae (r2 = 0.98). These results validate in silico usage of E-probes to detect the relative abundance variations in gut microbiota. Further in vitro validation will be performed to assess the microbial changes related to diet in nursery pigs.

scholarly journals Characteristics of hemolysins from pathogenic bacteria in tropical aquaculture: an in-silico study

2021 ◽  
Vol 890 (1) ◽  
pp. 012017
Author(s):  
Dewi Syahidah
Keyword(s):  
Blood Cells ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Protein Sequences ◽  
Host Cells ◽  
Bacterial Isolates ◽  
Damage Cell ◽  
In Silico Study ◽  
Tropical Aquaculture

Abstract Some species of known pathogenic bacteria isolates in tropical aquaculture produces hemolysin. Hemolysin can be identified based on its ability to break down red blood cells in vitro. Some hemolysin is a pore-shaped poison that can damage cell membranes and kill host cells. The character of the 13 sequences of hemolysin protein in several pathogenic bacterial isolates in tropical aquaculture was analysed using the NCBI protein bioinformatics database. The phylogenetic tree was generated, and the analysis was conducted using the base character method (Maximum Parsimony) of Mega 6.06 software. The result showed that there are two big family of hemolysin from the known pathogenic bacteria. The closest characteristics of protein sequences were hemolysin of Streptococcus agalacticae and of S. iniae.

scholarly journals Synthesis and Biological Evaluation of Lipophilic Nucleoside Analogues as Inhibitors of Aminoacyl-tRNA Synthetases

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 180
Author(s):  
Manesh Nautiyal ◽  
Bharat Gadakh ◽  
Steff De Graef ◽  
Luping Pang ◽  
Masroor Khan ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Metabolic Activation ◽  
Selective Inhibition ◽  
Biological Evaluation ◽  
Trna Synthetase ◽  
Bacterial Membranes ◽  
Trna Synthetases ◽  
Adenine Ring ◽  
Alkyl Moiety

Emerging antibiotic resistance in pathogenic bacteria and reduction of compounds in the existing antibiotics discovery pipeline is the most critical concern for healthcare professionals. A potential solution aims to explore new or existing targets/compounds. Inhibition of bacterial aminoacyl-tRNA synthetase (aaRSs) could be one such target for the development of antibiotics. The aaRSs are a group of enzymes that catalyze the transfer of an amino acid to their cognate tRNA and therefore play a pivotal role in translation. Thus, selective inhibition of these enzymes could be detrimental to microbes. The 5′-O-(N-(L-aminoacyl)) sulfamoyladenosines (aaSAs) are potent inhibitors of the respective aaRSs, however due to their polarity and charged nature they cannot cross the bacterial membranes. In this work, we increased the lipophilicity of these existing aaSAs in an effort to promote their penetration through the bacterial membrane. Two strategies were followed, either attaching a (permanent) alkyl moiety at the adenine ring via alkylation of the N6-position or introducing a lipophilic biodegradable prodrug moiety at the alpha-terminal amine, totaling eight new aaSA analogues. All synthesized compounds were evaluated in vitro using either a purified Escherichia coli aaRS enzyme or in presence of total cellular extract obtained from E. coli. The prodrugs showed comparable inhibitory activity to the parent aaSA analogues, indicating metabolic activation in cellular extracts, but had little effect on bacteria. During evaluation of the N6-alkylated compounds against different microbes, the N6-octyl containing congener 6b showed minimum inhibitory concentration (MIC) of 12.5 µM against Sarcina lutea while the dodecyl analogue 6c displayed MIC of 6.25 µM against Candida albicans.

Dioxybenzone triggers enhanced estrogenic effect via metabolic activation: in silico, in vitro and in vivo investigation

2021 ◽  
Vol 268 ◽  
pp. 115766
Author(s):  
Tingjie Zhan ◽  
Leili Zhang ◽  
Shixuan Cui ◽  
Weiping Liu ◽  
Ruhong Zhou ◽  
...  
Keyword(s):  
In Silico ◽  
Metabolic Activation ◽  
Estrogenic Effect

scholarly journals Antibacterial activity of endosymbiotic bacterial compound from Pheretima sp. earthworms inhibit the growth of Salmonella Typhi and Staphylococcus aureus: in vitro and in silico approach

2021 ◽  
Author(s):  
Dirayah Rauf Husain ◽  
Riuh Wardhani
Keyword(s):  
Antibacterial Activity ◽  
Binding Affinity ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Salmonella Typhi ◽  
Inhibition Test ◽  
Diffusion Method ◽  
Agar Diffusion ◽  
Potent Inhibition

Background and Objectives: Earthworms coexist with various pathogenic microorganisms; thus, their immunity mecha- nisms have developed through a long process of adaptation, including through endogenous bacterial symbionts. This study aims to identify earthworm endosymbiont bacteria compounds and their antibacterial activity through an in vitro approach supported by an in silico approach. Materials and Methods: This research was conducted using the in vitro inhibition test through agar diffusion and the in silico test using molecular docking applications, namely, PyRx and Way2Drugs Prediction of Activity Spectra for Substances (PASS). Results: The in vitro results showed a potent inhibition activity with a clear zone diameter of 21.75 and 15.5 mm for Staph- ylococcus aureus and Salmonella Typhi, respectively. These results are supported by chromatography and in silico tests, which showed that several compounds in endosymbiotic bacteria, cyclo (phenylalanyl-prolyl) and sedanolide, have high binding affinity values with several antibiotic-related target proteins in both pathogenic bacteria. Cyclo (phenylalanyl-prolyl) has the highest binding affinity of -6.0 to dihydropteroate synthase, -8.2 to topoisomerase, and -8.2 to the outer membrane, whereas sedanolide has the highest binding affinity to DNA gyrase with approximately -7.3. This antibiotic activity was also clarified through the Way2Drugs PASS application. Conclusion: Ten active compounds of endosymbiont bacteria, Cyclo (phenylalanyl-prolyl) and sedanolide were potential candidates for antibacterial compounds based on the inhibition test of the agar diffusion method and the results of reverse docking and Way2Drugs PASS.

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