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

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 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

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 Biofilms on Indwelling Urethral Catheters Produce Quorum-Sensing Signal Molecules In Situ and In Vitro

1998 ◽  
Vol 64 (9) ◽  
pp. 3486-3490 ◽  
Author(s):  
David J. Stickler ◽  
Nicola S. Morris ◽  
Robert J. C. McLean ◽  
Clay Fuqua
Keyword(s):  
Quorum Sensing ◽  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Feeding Assay ◽  
Gram Negative ◽  
Homoserine Lactones ◽  
Acylated Homoserine Lactones

ABSTRACT Acylated homoserine lactones (AHLs) are chemical signals that mediate population density-dependent (quorum-sensing) gene expression in numerous gram-negative bacteria. In this study, gram-negative bacilli isolated from catheters were screened for AHL production by a cross-feeding assay utilizing an AHL-responsive Agrobacterium tumefaciens reporter strain. Positive reactions were obtained from 14 isolates of Pseudomonas aeruginosa; negative or weakly positive reactions were recorded for isolates of five other species. P. aeruginosa biofilms were then produced on catheters in a physical model of the bladder. Sections of colonized all-silicone catheters gave positive reactions for the quorum-sensing signal molecules as did sections that had been cleaned of biofilm and autoclaved. Control sections of unused catheters were negative in the tests. Sections from four of nine catheters that had been freshly removed from patients gave positive reactions for AHLs. Cleaned autoclaved sections of three of these catheters also gave strongly positive reactions for AHLs. These results demonstrate that AHLs are produced by biofilms as they develop on the catheters both in vitro in the model and in vivo in the patient’s bladder. They represent the first demonstration of AHL production by biofilms in a clinical setting.

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.

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.

scholarly journals In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
The Other ◽  
Vitro Activity ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

Sign in / Sign up

Export Citation Format

Share Document