scholarly journals Coumarin Exhibits Broad-Spectrum Antibiofilm and Antiquorum Sensing Activity against Gram-Negative Bacteria: In Vitro and In Silico Investigation

ACS Omega ◽  
2021 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohammad Shavez Khan ◽  
Iqbal Ahmad ◽  
Fohad Mabood Husain ◽  
Rais Ahmad Khan ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Gram Negative Bacteria ◽  
Gram Negative

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties

2020 ◽  
Vol 18 (1) ◽  
pp. 591-607
Author(s):  
Hanan A. Althobiti ◽  
Sami A. Zabin
Keyword(s):  
Schiff Base ◽  
Metal Complexes ◽  
In Silico ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Schiff Base Ligands ◽  
Gram Positive ◽  
Gram Negative ◽  
Gi Absorption

AbstractThe purpose of this work was to prepare Schiff base ligands containing quinoline moiety and using them for preparing Cu(ii) and Zn(ii) complexes. Four bidentate Schiff base ligands (SL1–SL4) with quinoline hydrazine scaffold and a series of mononuclear Cu(ii) and Zn(ii) complexes were successfully prepared and characterized. The in vitro antibacterial and antifungal potential experimentation revealed that the ligands exhibited moderate antibacterial activity against the Gram-positive bacterial types and were inactive against the Gram-negative bacteria and the fungus strains. The metal complexes showed some enhancement in the activity against the Gram-positive bacterial strains and were inactive against the Gram-negative bacteria and the fungus strains similar to the parent ligands. The complex [Cu(SL1)2] was the most toxic compound against both Gram-positive S. aureus and E. faecalis bacteria. The in silico physicochemical investigation revealed that the ligand SL4 showed highest in silico absorption (82.61%) and the two complexes [Cu(SL4)2] and [Zn(SL4)2] showed highest in silico absorption with 56.23% for both compounds. The in silico pharmacokinetics predictions showed that the ligands have high gastrointestinal (GI) absorption and the complexes showed low GI absorption. The ligands showed a good bioavailability score of 0.55 where the complexes showed moderate to poor bioavailability.

In vitro and in silico evaluation of some plant extracts and phytocompounds against multidrug-resistant Gram-negative bacteria

2021 ◽  
Author(s):  
Eda Aydemir ◽  
Emrah Sarıyer ◽  
Esma Akyıldız ◽  
Azer Özad Düzgün ◽  
Yasemin Camadan ◽  
...  
Keyword(s):  
Plant Extracts ◽  
In Silico ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals In vitro antibacterial activity of essential oils from Lamiaceae species

2016 ◽  
Vol 5 (4) ◽  
pp. 141-144
Author(s):  
Vinod Kumar ◽  
◽  
C. S. Mathela ◽  
Amit Panwar ◽  
◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Essential Oils ◽  
Broad Spectrum ◽  
Antibacterial Effect ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Gram Negative ◽  
In Vitro Antibacterial Activity

Essential oils from Calamintha umbrosa and Nepeta species viz. N. leucophylla; N. hindostana; N. ciliaris and N. clarkei (family Lamiaceae), was tested against six bacterial strains. To evaluate the correlation between the antimicrobial activity and the essential oils, PCA and HCA analysis was done. PCA and HCA analysis of the antibacterial activity revealed that essential oils of Nepeta species had a strong and broad spectrum antibacterial effect against bacterial strains of P. aeruginosa and S. scandidus. The N. leucophylla oil showed higher activity against Gram-negative bacteria P. aeruginosa (10.5 mm, MIC 10 µL/mL) and K. pneumonia (9.1 mm, MIC 45 µL/mL) among all Nepeta oils which may be due to presence of active antimicrobial iridoids compounds.

Plumbagin inhibits quorum sensing-regulated virulence and biofilms of Gram-negative bacteria: in vitro and in silico investigations

Biofouling ◽  
2021 ◽  
pp. 1-16
Author(s):  
Faizan Abul Qais ◽  
Mohammad Shavez Khan ◽  
Iqbal Ahmad ◽  
Fohad Mabood Husain ◽  
Abdulaziz Abdullah Al-kheraif ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
In Silico ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals Flavonoid-Coated Gold Nanoparticles as Efficient Antibiotics against Gram-Negative Bacteria—Evidence from In Silico-Supported In Vitro Studies

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 968
Author(s):  
Hani A. Alhadrami ◽  
Raha Orfali ◽  
Ahmed A. Hamed ◽  
Mohammed M Ghoneim ◽  
Hossam M. Hassan ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
In Silico ◽  
Biological Activities ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Ic50 Values ◽  
Membrane Rigidity ◽  
Further Development

Flavonoids are a class of bioactive plant-derived natural products that exhibit a broad range of biological activities, including antibacterial ones. Their inhibitory activity toward Gram-positive bacterial was found to be superior to that against Gram-negative ones. In the present study, a number of flavonoid-coated gold nanoparticles (GNPs) were designed to enhance the antibacterial effects of chrysin, kaempferol, and quercetin against a number of Gram-negative bacteria. The prepared GNPs were able to conjugate to these three flavonoids with conjugation efficiency ranging from 41% to 80%. Additionally, they were able to exert an enhanced antibacterial activity in comparison with the free flavonoids and the unconjugated GNPs. Quercetin-coated GNPs were the most active nano-conjugates and were able to penetrate the cell wall of E. coli. A number of in silico experiments were carried out to explain the conjugation efficiency and the antibacterial mechanisms of these flavonoids as follows: (i) these flavonoids can efficiently bind to the glutathione linker on the surface of GNPs via H-bonding; (ii) these flavonoids, particularly quercetin, were able to increase the bacterial membrane rigidity, and hence decrease its functionality; (iii) these flavonoids can inhibit E. coli’s DNA gyrase (Gyr-B) with IC50 values ranging from 0.9 to 3.9 µM. In conclusion, these bioactive flavonoid-based GNPs are considered to be very promising antibiotic candidates for further development and evaluation.

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.

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 Cyanuric Chloride Containing Chalcones for Possible Breast Cancer Treatment: Synthesis, Antimicrobial and in silico Screening

2019 ◽  
Vol 32 (2) ◽  
pp. 408-414
Author(s):  
Revathy Selvaraj ◽  
J. Suresh ◽  
A. Arun
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Topoisomerase Ii ◽  
Excellent Result ◽  
Screening Method ◽  
Cyanuric Chloride ◽  
Gram Negative Bacteria ◽  
In Silico Screening ◽  
Gram Negative ◽  
Mic Value

In this work, we have synthesized efficient antibacterial compounds with anticancer novel molecules based on cyanuric chloride containing chalcone moiety. For this, novel triazine-based organic molecules were synthesized by using cyanuric chloride and 2,4-dichloro-1-ene(4-hydroxyphenyl)phenone and characterized by elemental analysis, FT-IR, NMR and UV-visible spectrometry techniques. Melting point of the molecules were increased with an increase in substitution on cyanuric chloride. The minimum inhibitory concentration (MIC) value of the synthesized compounds showed an excellent result on Gram-negative bacteria with low MIC value of 1.95 μg/mL. Gram-positive bacteria showed little resistance to the synthesized drug. The synthesized compounds were tested for their use as an anticancer drug using in silico screening method. The synthesized compounds in silico molecular docking method using breast cancer protein (BRCA2) confirms that triazine derivative with all three chlorine molecules replaced by 2,4-dichloro-1-ene(4-hydroxyphenyl)phenone showed highest binding energy with the value of -9.1900 Kcal/mol which is in agreement with the observed high MIC value obtained for Gram-negative bacteria. The synthesized molecules preferentially targeted the topoisomerase II of the bacteria. Overall, an efficient antimicrobial drug is synthesized using a simple preparation method.

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