Virtual screening of antibacterial compounds by similarity search of Enoyl-ACP reductase (FabI) inhibitors

2020 ◽  
Vol 12 (1) ◽  
pp. 51-68 ◽  
Author(s):  
Leonardo Rander Asse Junior ◽  
Thales Kronenberger ◽  
Mateus Sá Magalhães Serafim ◽  
Yamara Viana Sousa ◽  
Isabella Drumond Franco ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Virtual Screening ◽  
Therapeutic Potential ◽  
Structural Similarity ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Enoyl Acp Reductase ◽  
Potential Inhibitors ◽  
New Compounds ◽  
Development Methods

Aim: Antibiotic resistance is an alarming issue, as multidrug-resistant bacteria are growing worldwide, hence the decrease of therapeutic potential of available antibiotic arsenal. Among these bacteria, Staphylococcus aureus was pointed by the WHO in the pathogens list to be prioritized in drug development. Methods: We report the use of chemical similarity models for the virtual screening of new antibacterial with structural similarity to known inhibitors of FabI. The potential inhibitors were experimentally evaluated for antibacterial activity and membrane disrupting capabilities. Results & conclusion: These models led to the finding of four new compounds with antibacterial activity, one of which having antimicrobial activity already reported in the literature.

scholarly journals Phytochemical Screening and Potential Antibacterial Activity of Defatted and Nondefatted Methanolic Extracts of Xao Tam Phan (Paramignya trimera (Oliv.) Guillaum) Peels against Multidrug-Resistant Bacteria

Scientifica ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Van-Anh Le Thi ◽  
Ngoc-Lien Nguyen ◽  
Quang-Huy Nguyen ◽  
Quyen Van Dong ◽  
Thi-Yen Do ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Herbal Medicine ◽  
High Resolution Mass Spectrometry ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Limited Information ◽  
Isolation And Identification ◽  
Methanolic Extracts ◽  
The Difference ◽  
New Compounds

Xao tam phan (Paramignya trimera (Oliv.) Guillaum) is a traditional herbal medicine in Vietnam. Previous investigations reported mainly compounds and bioactivities of roots, stems, and leaves while there is limited information about those of fruits. This study aims to reveal the difference in the chemical profile of defatted peel (DP) and nondefatted peel (NDP) methanolic extracts of P. trimera using colorimetric reactions and liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) analysis. We also showed the potential antibacterial activity of two extracts against clinically isolated bacteria strains including P. aeruginosa, Salmonella sp., and S. aureus with the MIC values < 100 μg/mL. This preliminary result proves the traditional usage of this herbal medicine and can be helpful for further investigation on the isolation and identification of the new compounds in P. trimera peels.

scholarly journals Antibacterial Activity of Moroccan Zantaz Honey and the Influence of Its Physicochemical Parameters Using Chemometric Tools

2021 ◽  
Vol 11 (10) ◽  
pp. 4675
Author(s):  
Youssef Elamine ◽  
Hamada Imtara ◽  
Maria Graça Miguel ◽  
Ofélia Anjos ◽  
Letícia M. Estevinho ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Properties ◽  
Principal Component ◽  
Physicochemical Characteristics ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Coumaric Acid ◽  
Atlas Mountains ◽  
Methyl Syringate ◽  
Chemometric Tools

The emergence of multidrug-resistant bacteria has prompted the development of alternative therapies, including the use of natural products with antibacterial properties. The antibacterial properties of Zantaz honey produced in the Moroccan Atlas Mountains against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus was evaluated and analyzed using chemometric tools. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against S. aureus were the lowest (112.5 ± 54.5 mg/mL), revealing that this species was most sensitive to Zantaz honey. P. aeruginosa showed an intermediate sensitivity (MIC= 118.75 ± 51.9 mg/mL), while E. coli was the most resistant to treatment (MIC = 175 ± 61.2 mg/mL). Content of monosaccharides, certain minerals, and phenolic compounds correlated with antibacterial activity (p < 0.05). Principal component analysis of physicochemical characteristics and antibacterial activity indicated that the parameters most associated with antibacterial activity were color, acidity, and content of melanoidins, fructose, epicatechin, methyl syringate, 4-coumaric acid, and 3-coumaric acid.

scholarly journals The Antibacterial Activity of Human Amniotic Membrane against Multidrug-Resistant Bacteria Associated with Urinary Tract Infections: New Insights from Normal and Cancerous Urothelial Models

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 218
Author(s):  
Taja Železnik Ramuta ◽  
Larisa Tratnjek ◽  
Aleksandar Janev ◽  
Katja Seme ◽  
Marjanca Starčič Erjavec ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Amniotic Membrane ◽  
Multidrug Resistant ◽  
Basic Knowledge ◽  
Resistant Bacteria ◽  
Human Amniotic Membrane ◽  
Multidrug Resistant Bacteria ◽  
Tract Infections

Urinary tract infections (UTIs) represent a serious global health issue, especially due to emerging multidrug-resistant UTI-causing bacteria. Recently, we showed that the human amniotic membrane (hAM) could be a candidate for treatments and prevention of UPEC and Staphylococcus aureus infections. However, its role against multidrug-resistant bacteria, namely methicillin-resistant S. aureus (MRSA), extended-spectrum beta-lactamases (ESBL) producing Escherichia coli and Klebsiella pneumoniae, vancomycin-resistant Enterococci (VRE), carbapenem-resistant Acinetobacter baumannii, and Pseudomonas aeruginosa has not yet been thoroughly explored. Here, we demonstrate for the first time that the hAM homogenate had antibacterial activity against 7 out of 11 tested multidrug-resistant strains, the greatest effect was on MRSA. Using novel approaches, its activity against MRSA was further evaluated in a complex microenvironment of normal and cancerous urinary bladder urothelia. Even short-term incubation in hAM homogenate significantly decreased the number of bacteria in MRSA-infected urothelial models, while it did not affect the viability, number, and ultrastructure of urothelial cells. The hAM patches had no antibacterial activity against any of the tested strains, which further exposes the importance of the hAM preparation. Our study substantially contributes to basic knowledge on the antibacterial activity of hAM and reveals its potential to be used as an antibacterial agent against multidrug-resistant bacteria.

Design, synthesis and antibacterial evaluation of ocotillol derivatives with polycyclic nitrogen-containing groups

2021 ◽  
Author(s):  
Yucheng Cao ◽  
Kaiyi Wang ◽  
Jiali Wang ◽  
Haoran Cheng ◽  
Mengxin Ma ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
Design Synthesis ◽  
In Vitro Antibacterial Activity ◽  
Strong Inhibitory Effect ◽  
Hospital Acquired ◽  
Derivatives Of

Aim: With the increasing abuse of antibacterial drugs, multidrug-resistant bacteria have become a burden on human health and the healthcare system. To find alternative compounds effective against hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA), novel derivatives of ocotillol were synthesized. Methods & Results: Ocotillol derivatives with polycyclic nitrogen-containing groups were synthesized and evaluated for in vitro antibacterial activity. Compounds 36–39 exhibited potent antibacterial activity against hospital-acquired MRSA, with MIC = 8–64 μg/ml. Additionally, a combination of compound 37 and the commercially available antibiotic kanamycin showed synergistic inhibitory effects, with a fractional inhibitory concentration index of ≤0.375. Conclusion: Compound 37 has a strong inhibitory effect, and this derivative has potential for use as a pharmacological tool to explore antibacterial mechanisms.

scholarly journals Engineered Lysins With Customized Lytic Activities Against Enterococci and Staphylococci

2020 ◽  
Vol 11 ◽  
Author(s):  
Hana Sakina Binte Muhammad Jai ◽  
Linh Chi Dam ◽  
Lowella Servito Tay ◽  
Jodi Jia Wei Koh ◽  
Hooi Linn Loo ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Catalytic Domain ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Species Specificity ◽  
Resistant Bacteria ◽  
Modular Architecture ◽  
Narrow Spectrum ◽  
Cell Wall Binding ◽  
Peptidoglycan Hydrolysis

The emergence of multidrug-resistant bacteria has made minor bacterial infections incurable with many existing antibiotics. Lysins are phage-encoded peptidoglycan hydrolases that have demonstrated therapeutic potential as a novel class of antimicrobials. The modular architecture of lysins enables the functional domains – catalytic domain (CD) and cell wall binding domain (CBD) – to be shuffled to create novel lysins. The CD is classically thought to be only involved in peptidoglycan hydrolysis whereas the CBD dictates the lytic spectrum of a lysin. While there are many studies that extended the lytic spectrum of a lysin by domain swapping, few have managed to introduce species specificity in a chimeric lysin. In this work, we constructed two chimeric lysins by swapping the CBDs of two parent lysins with different lytic spectra against enterococci and staphylococci. We showed that these chimeric lysins exhibited customized lytic spectra distinct from the parent lysins. Notably, the chimeric lysin P10N-V12C, which comprises a narrow-spectrum CD fused with a broad-spectrum CBD, displayed species specificity not lysing Enterococcus faecium while targeting Enterococcus faecalis and staphylococci. Such species specificity can be attributed to the narrow-spectrum CD of the chimeric lysin. Using flow cytometry and confocal microscopy, we found that the E. faecium cells that were treated with P10N-V12C are less viable with compromised membranes yet remained morphologically intact. Our results suggest that while the CBD is a major determinant of the lytic spectrum of a lysin, the CD is also responsible in the composition of the final lytic spectrum, especially when it pertains to species-specificity.

Stalobacin: Discovery of Novel Lipopeptide Antibiotics with Potent Antibacterial Activity against Multidrug-Resistant Bacteria

2020 ◽  
Vol 63 (11) ◽  
pp. 6090-6095 ◽  
Author(s):  
Kouhei Matsui ◽  
Yukiko Kan ◽  
Junko Kikuchi ◽  
Keisuke Matsushima ◽  
Miki Takemura ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Lipopeptide Antibiotics

scholarly journals 5-Arylideneimidazolones with Amine at Position 3 as Potential Antibiotic Adjuvants against Multidrug Resistant Bacteria

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 438 ◽  
Author(s):  
Aneta Kaczor ◽  
Karolina Witek ◽  
Sabina Podlewska ◽  
Joanna Czekajewska ◽  
Annamaria Lubelska ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Enterobacter Aerogenes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Aromatic Rings ◽  
Efflux Pump Inhibitor ◽  
Fold Reduction ◽  
Dual Action ◽  
New Compounds

Searching for new chemosensitizers of bacterial multidrug resistance (MDR), chemical modifications of (Z)-5-(4-chlorobenzylidene)-2-(4-methylpiperazin-1-yl)-3H-imidazol-4(5H)-one (6) were performed. New compounds (7–17), with fused aromatic rings at position 5, were designed and synthesized. Crystallographic X-ray analysis proved that the final compounds (7–17) were substituted with tertiary amine-propyl moiety at position 3 and primary amine group at 2 due to intramolecular Dimroth rearrangement. New compounds were evaluated on their antibiotic adjuvant properties in either Gram-positive or Gram-negative bacteria. Efflux pump inhibitor (EPI) properties towards the AcrAB-TolC pump in Enterobacter aerogenes (EA289) were investigated in the real-time efflux (RTE) assay. Docking and molecular dynamics were applied to estimate an interaction of compounds 6–17 with penicillin binding protein (PBP2a). In vitro ADME-Tox properties were evaluated for compound 9. Most of the tested compounds reduced significantly (4-32-fold) oxacillin MIC in highly resistant MRSA HEMSA 5 strain. The anthracene-morpholine derivative (16) was the most potent (32-fold reduction). The tested compounds displayed significant EPI properties during RTE assay (37–97%). The naphthyl-methylpiperazine derivative 9 showed the most potent “dual action” of both oxacillin adjuvant (MRSA) and EPI (E. aerogenes). Molecular modeling results suggested the allosteric mechanism of action of the imidazolones, which improved binding of oxacillin in the PBP2a active site in MRSA.

scholarly journals Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening

2019 ◽  
Vol 12 (1) ◽  
pp. 20 ◽  
Author(s):  
Ryan Ramos ◽  
Josivan Costa ◽  
Rai Silva ◽  
Glauber da Costa ◽  
Alex Rodrigues ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Binding Free Energy ◽  
Structural Similarity ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Biological Insecticide ◽  
Pass Online ◽  
Acetylcholinesterase Enzyme ◽  
Potential Inhibitors

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of −10.5 and −10.3 kcal/mol, respectively. The interaction with the juvenile hormone was −11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.

scholarly journals Antibacterial Activity of Defatted and Nondefatted Methanolic Extracts of Aframomum melegueta K. Schum. against Multidrug-Resistant Bacteria of Clinical Importance

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Olufunmiso Olusola Olajuyigbe ◽  
Otunola Adedayo ◽  
Roger Murugas Coopoosamy
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Methanol Extract ◽  
Clinical Importance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Plant Materials ◽  
Methanolic Extracts ◽  
Agar Dilution ◽  
Inhibition Zones

The antibacterial activity of the extracts of Aframomum melegueta including n-hexane extract (NHE), nondefatted methanol extract (NDME), and defatted methanol extract (DME) was investigated in this study. The NHE exhibited no antibacterial activity. The DME showed higher antibacterial activity than the NDME against the different isolates. At the highest concentration of 10 mg/mL in agar diffusion, NDME produced inhibition zones ranging from 11 to 29 mm against the microorganisms while DME produced inhibition zones ranging from 20 to 40 mm with the concentration of 10 mg/mL against the microorganisms. 0.1 mg/mL of the DME produced inhibition zones ranging between 12 and 14 mm in Aeromonas hydrophila ATCC 35654 and Pseudomonas aeruginosa ATCC 15442, respectively, while none of the isolates were inhibited by the NDME at a concentration of 1 mg/mL or less. In the agar dilution assay, the MICs of the NDME and DME ranged between 0.31 and 10 mg/mL, but more isolates were inhibited at 0.31 mg/mL of DME than those in NDME. In macrobroth assay, the MICs of the NDME ranged between 0.15 and 5.0 mg/mL and the MBCs ranged between 0.63 and 5.0 mg/mL, and the MICs of the DME ranged between 0.08 and 5.0 mg/mL and the MBCs were between 0.31 and 5.0 mg/mL. This study indicated that DME was more active with higher antibacterial activity than the NDME of this plant, and extracting the fatty portion of plant materials prior susceptibility testing would allow plant extracts to be more effective as well as justifying the use of Aframomum melegueta in traditional medicine for the treatment of bacterial infections.

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