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 Antimicrobial efficacy of a new tri-antibiotic combination against resistant endodontic pathogens: An in-vitro study

2020 ◽  
Vol 23 (4) ◽  
pp. 8p ◽  
Author(s):  
Prasanna T. Dahake ◽  
Sudhindra M Baliga
Keyword(s):  
Root Canal ◽  
Pathogenic Bacteria ◽  
Culture Media ◽  
In Vitro Study ◽  
Vitro Study ◽  
New Combination ◽  
Antimicrobial Efficacy ◽  
E Coli ◽  
Background Removal

Background: Removal of all the pathogenic bacteria from the root canal system is of prime importance for the success of endodontic therapy. Objective: The study aimed to determine the antimicrobial efficacy of three antibiotics and their new combination against selected endodontic pathogens. Methods: In this in-vitro study, we used bacterial strains associated with the refractory endodontic condition and determined MIC and MBC of Clindamycin (C), Metronidazole (M), Doxycycline (D) as well as their combination CMD. We cultured Candida Albicans, Pseudomonas Aeruginosa, Escherichia Coli, Enterococcus Faecalis, Streptococcus Mutans, Bacillus Subtilis subsp. spizizenii, Actinomyces Actinomycetemcomitans on selective culture media. We analyzed the data using paired 't' test, one-way ANOVA, and Tuckey's HSD post hoc test. Results: Clindamycin inhibited the growth of C. Albicans (90%) and S. Mutans (90%) significantly and P. Aeruginosa, E. Coli, E. Faecalis, B. Subtilis, and A. Actinomycetemcomitans were resistant to it. Metronidazole did not inhibit any of the bacteria. Doxycycline inhibited C. Albicans (90%), P. Aeruginosa (90%), and S. Mutans (90%) significantly while E. Coli, E. Faecalis, B. Subtilis, and A. Actinomycetemcomitans were resistant to it. The combination of CMD inhibited all the microbes significantly. However, at bactericidal concentrations of CMD, E. Faecalis (p = 0.024), B. Subtilis (p = 0.021) and A. Actinomycetemcomitans (p = 0.041) were eliminated significantly, while C. Albicans (p = 0.164), P. Aeruginosa (p = 0.489), E. Coli (p = 0.106) and S. Mutans (p = 0.121) showed resistance. Conclusion: Combination CMD can be used against resistant endodontic pathogens to achieve predictable endodontic results.KEYWORDSAntimicrobial agents; Clindamycin; Doxycycline; Metronidazole; Root canal therapy.    

scholarly journals Synthesis, in vitro Antimicrobial Evaluation, Molecular Docking Studies and ADME Prediction of Furan-2-yl-Morpholinophenylpyrimidine Derivatives

2021 ◽  
Vol 33 (5) ◽  
pp. 1090-1098
Author(s):  
M.R. Ezhilarasi ◽  
A.B. Senthieel Khumar ◽  
P. Elavarasan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
In Silico Docking ◽  
E Coli ◽  
Biological Studies ◽  
Antimicrobial Evaluation ◽  
Microbial Strains ◽  
In Silico Molecular Docking

A new series of novel 4-(furan-2-yl)-6-(4-morpholinophenyl)pyrimidine-amines (4a-c) were synthesized and characterized by elemental analysis and spectral analysis like IR, 1D 1H & 13C NMR. The synthesized compounds 4a-c were evaluated for their biological studies. The zone of inhibitions were examined for synthesized compounds 4a-c besides the identical set of microbial strains, especially that compound 4a against S. aureus, S. pyogenes, E. coli, compound 4b against P. aeruginosa has excellent antibacterial activity. Compound 4c shows good inhibition against C. albicans. Also in silico molecular docking and ADME predictions were carried for all the compounds. The docking studies were examined by two different proteins like 1UAG protein and 1OQA protein. in silico docking provides of the compounds have good docking score compared with the standard. In the ADME predictions all the compounds were met criteria. The synthesized compounds all of them obeyed the drug-likeness properties.

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.

scholarly journals Antimicrobial Activity of Selected Essential Oils against Selected Pathogenic Bacteria: In Vitro Study

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 546
Author(s):  
Nikola Puvača ◽  
Jovana Milenković ◽  
Tamara Galonja Galonja Coghill ◽  
Vojislava Bursić ◽  
Aleksandra Petrović ◽  
...  
Keyword(s):  
Gas Chromatography ◽  
Antimicrobial Activity ◽  
Essential Oil ◽  
Essential Oils ◽  
Pathogenic Bacteria ◽  
Antimicrobial Properties ◽  
In Vitro Study ◽  
Tea Tree ◽  
E Coli

The worldwide problem of infectious diseases has appeared in recent years, and antimicrobial agents are crucial in reducing disease emergence. Nevertheless, the development and distribution of multidrug-resistant (MDR) strains in pathogenic bacteria, such as Escherichia coli, Staphylococcus aureus, Salmonella Typhi and Citrobacter koseri, has become a major society health hazard. Essential oils could serve as a promising tool as a natural drug in fighting the problem with these bacteria. The current study aimed to investigate the antimicrobial effectiveness of tea tree (Melaleuca alternifolia (Maiden and Betche) Cheel), rosemary (Rosmarinus officinalis L.), eucalyptus (Eucalyptus obliqua L’Hér.), and lavender (Lavandula angustifolia Mill) essential oils. The antimicrobial properties of essential oils were screened against four pathogenic bacteria, E. coli, S. aureus, S. Tyhpi, and C. koseri, and two reference bacterial strains, while for the testing, the agar well diffusion method was used. Gas chromatography (GC) and gas chromatography–mass spectrometric (GC–MSD) analyses were performed on essential oils. The obtained results showed that M. alternifolia essential oil is the richest in terpinen-4-ol, R. officinalis and E. oblique essential oils in 1,8-cineole, and L. angustifolia essential oil in α-terpinyl acetate. In addition, the main bioactive compounds present in the essential oil of tea tree are rich in α-pinene (18.38%), limonene (7.55%) and γ-terpinene (14.01%). The essential oil of rosemary is rich in α-pinene (8.38%) and limonene (11.86%); eucalyptus essential oil has significant concentrations of α-pinene (12.60%), p-cymene (3.24%), limonene (3.87%), and γ-terpinene (7.37%), while the essential oil of lavender is rich in linalool (10.71%), linalool acetate (9.60%), α-terpinyl acetate (10.93%), and carbitol (13.05%) bioactive compounds, respectively. The obtained results from the in vitro study revealed that most of the essential oils exhibited antimicrobial properties. Among the tested essential oils, tea tree was discovered to demonstrate the strongest antimicrobial activity. The recorded MIC of S. Typhi was 6.2 mg/mL, 3.4 mg/mL of C. koseri, 3.1 mg/mL of E. coli, and 2.7 mg/mL of E. Coli ATCC 25922, compared to M. alternifolia. Similarly, only S. aureus ATCC 25923 showed antimicrobial activity towards R. officinalis (1.4 mg/mL), E. oblique (2.9 mg/mL), and L. angustifolia (2.1 mg/mL). Based on the obtained results, it is possible to conclude that tea tree essential oil might be used as an ecological antimicrobial in treating infectious diseases caused by the tested pathogens.

scholarly journals A Evaluate the biological activity of Citrullus Colocynthis extract (In vitro study)

2021 ◽  
Vol 26 (4) ◽  
Author(s):  
HAYDER YOUSIF ◽  
Zahraa F Shaker ◽  
Hayder Hamed Abed
Keyword(s):  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Antibacterial Properties ◽  
Water Extract ◽  
In Vitro Study ◽  
Ethanolic Extract ◽  
Citrullus Colocynthis ◽  
E Coli ◽  
Test Organisms

The plant of c. colocynthis is perennial herbal of the Cucurbitaceous types that isused as a traditional medicinal plant on a Mediterranean tub and equatorialnations.Studies on the antibacterial properties of Citrullus colocynthis leaf extract,Medicinal plants have conventional been used in abortifacient and treatsconstipation, edema, Infection caused by bacteria, cancer and diabetesproblems.The antibacterial efficacy of citrullus colocynthesis (L.) was investigatedin this work using five species of pathogenic bacteria isolated from urinary tractinfections: E. coli, Klebsiella pneumoniae, Streptococcus spp, Psudomonasauroginosa, and Staphylococcus aureus. For the antibacterial test, water andethanol extract were employed.The ethanolic extract showed inhibitory activityagainst Escherichia Coli at (100 °C, 80 °C, 60 °C) while Staphylococcus aureus at(100 °C, 80 °C), Streptococcus spp. at (100 °C). Water extract exhibited less or noactivity against all types of bacteria.The findings of this investigation indicate thatC. colocynthis might be utilized to treat disorders caused by the test organisms.

Preliminary in Vitro Investigations on The Inhibitory Activity of The Original Dietary Supplement Oxidal® on Pathogenic Bacterial Strains

2020 ◽  
Vol 11 ◽  
pp. 37-43
Author(s):  
Prof. Teodora P. Popova ◽  
Toshka Petrova ◽  
Ignat Ignatov ◽  
Stoil Karadzhov
Keyword(s):  
Dietary Supplement ◽  
Broad Spectrum ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Clinical Effectiveness ◽  
Inhibitory Effect ◽  
Diffusion Method ◽  
Bacterial Strains ◽  
Microbial Strains

The antimicrobial action of the dietary supplement Oxidal® was tested using the classic Bauer and Kirby agar-gel diffusion method. Clinical and reference strains of Staphylococcus aureus and Escherichia coli were used in the studies. The tested dietary supplement showed a well-pronounced inhibitory effect against the microbial strains commensurable with that of the broad-spectrum chemotherapeutic agent Enrofloxacin and showed even higher activity than the broad spectrum antibiotic Thiamphenicol. The proven inhibitory effect of the tested dietary supplement against the examined pathogenic bacteria is in accordance with the established clinical effectiveness standards for antimicrobial agents.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Repurposing of auranofin against bacterial infections: An In silico and In vitro study

2020 ◽  
Vol 16 ◽  
Author(s):  
Nidhi Sharma ◽  
Arti Singh ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Antibacterial Agent ◽  
Bacterial Infections ◽  
In Vitro Assays ◽  
Infection Model ◽  
Synergistic Activity ◽  
Bacterial Strains ◽  
Molecular Docking Study

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software). Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin. Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

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