scholarly journals Compound Prioritization through Meta-Analysis Enhances the Discovery of Antimicrobial Hits against Bacterial Pathogens

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1065
Author(s):  
Loic Deblais ◽  
Gireesh Rajashekara
Keyword(s):  
Antimicrobial Activity ◽  
Drug Discovery ◽  
In Silico ◽  
Plant Pathogens ◽  
Bacterial Pathogens ◽  
Meta Analysis ◽  
Chemical Properties ◽  
Molar Refraction ◽  
In Silico Model ◽  
Future Drug

The development of informatic tools to improve the identification of novel antimicrobials would significantly reduce the cost and time of drug discovery. We previously screened several plant (Xanthomonas sp., Clavibacter sp., Acidovorax sp., and Erwinia sp.), animal (Avian pathogenic Escherichia coli and Mycoplasma sp.), and human (Salmonella sp. and Campylobacter sp.) pathogens against a pre-selected small molecule library (n = 4182 SM) to identify novel SM (hits) that completely inhibited the bacterial growth or attenuated at least 75% of the virulence (quorum sensing or biofilm). Our meta-analysis of the primary screens (n = 11) using the pre-selected library (approx. 10.2 ± 9.3% hit rate per screen) demonstrated that the antimicrobial activity and spectrum of activity, and type of inhibition (growth versus virulence inhibitors) correlated with several physico-chemical properties (PCP; e.g., molecular weight, molar refraction, Zagreb group indexes, Kiers shape, lipophilicity, and hydrogen bond donors and acceptors). Based on these correlations, we build an in silico model that accurately classified 80.8% of the hits (n = 1676/2073). Therefore, the pre-selected SM library of 4182 SM was narrowed down to 1676 active SM with predictable PCP. Further, 926 hits affected only one species and 1254 hits were active against specific type of pathogens; however, no correlation was detected between PCP and the type of pathogen (29%, 34%, and 46% were specific for animal, human foodborne and plant pathogens, respectively). In conclusion, our in silico model allowed rational identification of SM with potential antimicrobial activity against bacterial pathogens. Therefore, the model developed in this study may facilitate future drug discovery efforts by accelerating the identification of uncharacterized antimicrobial molecules and predict their spectrum of activity.

scholarly journals Anti-cancer and Antimicrobial Activity, In-Silico ADME and Docking Studies of Biphenyl Pyrazoline Derivatives

2020 ◽  
Vol 11 (1) ◽  
pp. 8266-8282
Keyword(s):  
Breast Cancer ◽  
Antimicrobial Activity ◽  
Binding Affinity ◽  
In Silico ◽  
Chemical Properties ◽  
Cancer Cell Line ◽  
Docking Studies ◽  
Spectral Studies ◽  
Compound 21 ◽  
Affinity Score

The present study deals with the multicomponent Michal addition reaction of xenyl chalcone (10-17) reacting with hydrazine hydrate in the presence of ethane carboxylic acid. It afforded new pyrazoline compounds. The propane pyrazoline derivatives (18-25) skeleton structure was confirmed by spectral studies like Fourier-Transform Infrared spectroscopy, 1H NMR, 13C NMR, and CHN analysis. The adsorption, distribution, metabolism, and excretion (ADME) properties of the synthesized molecules were investigated. The results obtained in-silico demonstrated that these molecules could be considered as orally active drug candidates due to their physical and chemical properties. The compounds (18-25) were subjected to docking prediction studies by protein (1UAG) and breast cancer protein (1OQA). While Comparing with the drug ciprofloxacin, among the series of eight compounds (18-25), compound 19, 20, and 24 have the best binding affinity score (-8.5 kcal/mol). We have selected only the compound 21 (4-Cl (electronegativity group)) compound for MTT assay of breast cancer cell line studies because it has the best binding affinity score in the binding study of the compound with 1OQA protein. Synthesized pyrazoline compound (18-25) also obeys the Lipinski rule of five and other criteria of drug-likeness properties. Among the synthesized pyrazoline compound (18-25), especially compound 21 (electronegativity group (4-Cl) has the best drug-likeness property and has a value of 7.16. Furthermore, antimicrobial activity of these compounds has been evaluated against five microbial strains, and from this result, some of the newly synthesized compounds exhibit good activity.

scholarly journals Broad spectrum antimicrobial activities from spore-forming bacteria isolated from the Vietnam Sea

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10117
Author(s):  
Khanh Minh Chau ◽  
Dong Van Quyen ◽  
Joshua M. Fraser ◽  
Andrew T. Smith ◽  
Thi Thu Hao Van ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Bacterial Pathogens ◽  
Paenibacillus Polymyxa ◽  
Antimicrobial Activities ◽  
Antimicrobial Compounds ◽  
Antibiotic Resistant ◽  
Future Drug ◽  
Spore Forming Bacteria

The widespread occurrence of pathogenic bacteria resistant to last-line antibiotics has resulted in significant challenges in human and veterinary medicine. There is an urgent need for new antimicrobial agents that can be used to control these life threating pathogens. We report the identification of antimicrobial activities, against a broad range of bacterial pathogens, from a collection of marine-derived spore-forming bacteria. Although marine environments have been previously investigated as sources of novel antibiotics, studies on such environments are still limited and there remain opportunities for further discoveries and this study has used resources derived from an under-exploited region, the Vietnam Sea. Antimicrobial activity was assessed against a panel of Gram-positive and Gram-negative bacteria, including several multi-drug resistant pathogens. From a total of 489 isolates, 16.4% had antimicrobial activity. Of 23 shortlisted isolates with the greatest antimicrobial activity, 22 were Bacillus spp. isolates and one was a Paenibacillus polymyxa isolate. Most of the antimicrobial compounds were sensitive to proteases, indicating that they were proteins rather than secondary metabolites. The study demonstrated that marine bacteria derived from the Vietnam Sea represent a rich resource, producing antimicrobial compounds with activity against a broad range of clinically relevant bacterial pathogens, including important antibiotic resistant pathogens. Several isolates were identified that have particularly broad range activities and produce antimicrobial compounds that may have value for future drug development.

The Study of Bacillus Subtils Antimicrobial Activity on Some of the Pathological Isolates

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Hussein A Kadhum ◽  
Thualfakar H Hasan2
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Bacillus Subtilis ◽  
Bacterial Growth ◽  
Broad Spectrum ◽  
Inhibitory Activity ◽  
Bacterial Pathogens ◽  
Inhibitory Ability ◽  
Selection Of

The study involved the selection of two isolates from Bacillus subtilis to investigate their inhibitory activity against some bacterial pathogens. B sub-bacteria were found to have a broad spectrum against test bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. They were about 23-30 mm and less against Klebsiella sp. The sensitivity of some antibodies was tested on the test samples. The results showed that the inhibitory ability of bacterial growth in the test samples using B. subtilis extract was more effective than the antibiotics used.

Design, Synthesis and Docking Studies of Some Novel Fluoroquinolone Compounds with Antibacterial Activity

2018 ◽  
Vol 69 (4) ◽  
pp. 815-822 ◽  
Author(s):  
Lucia Pintilie ◽  
Amalia Stefaniu ◽  
Alina Ioana Nicu ◽  
Maria Maganu ◽  
Miron Teodor Caproiu
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Drug Discovery ◽  
Elemental Analysis ◽  
Docking Studies ◽  
Receptor Protein ◽  
Chemical Methods ◽  
Design Synthesis ◽  
Gram Negative

A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compounds have been characterized by physic-chemical methods (elemental analysis, FTIR, NMR, UV-Vis) and by antimicrobial activity against Gram-positive and Gram-negative microorganisms. For the synthesized compounds have been performed calculations of characteristics and molecular properties, using Spartan�14 Software from Wavefunction, Inc. Irvine, CA. and molecular docking studies using CLC Drug Discovery Workbench 2.4 software, to identify and visualize the most likely interaction ligand (fluoroquinolone) with the receptor protein.

Synthesis, SAR, In-Silico appraisal and Anti-Microbial Study of substituted 2-aminobenzothiazoles derivatives

2019 ◽  
Vol 15 ◽  
Author(s):  
Devidas G. Anuse ◽  
Suraj N. Mali ◽  
Bapu R. Thorat ◽  
Ramesh S. Yamgar ◽  
Hemchandra K. Chaudhari
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Docking Study ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Mass Spectral ◽  
Gram Positive Bacteria ◽  
Ft Ir ◽  
In Silico Molecular Docking

Background: Antimicrobial resistance is major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. Methods: All synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. Results: The compounds 3d and 3h were showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in-silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. Conclusion: Our current study would definitely pave the new way towards designing and synthesis of more potent 2-aminobenzothiazoles derivatives.

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