Moxifloxacin derivatives with potential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)

Background: Methicillin-resistant S. aureus (MRSA) has already tormented humanity and the environment for a long time and is responsible for many difficult-to-treat infections. Unfortunately, there are limited therapeutic options, and MRSA isolates with complete resistance to vancomycin, the first-line drug for the treatment of MRSA infections, have already emerged in recent years. Moxifloxacin retained activity against mutant bacterial strains with various levels of fluoroquinolones resistance and had a lower potential to select for resistant mutants. Isatin is a versatile structure, and its derivatives are potent inhibitors of many enzymes and receptors. The fluoroquinolone-isatin derivatives demonstrated excellent antibacterial activity against both drug-sensitive and drug-resistant organisms. The structure-activity relationship elucidated that incorporation of 1,2,3-triazole moiety into the C-7 position of fluoroquinolone skeleton was favorable to the antibacterial activity. Accordingly, fluoroquinolone derivatives with isatin and 1,2,3-triazole fragments at the side chain on the C-7 position are promising candidates to fight against drug-resistant bacteria. Objective: To explore more active moxifloxacin derivatives to fight against MRSA and enrich the structure-activity relationships. Methods: The synthesized moxifloxacin derivatives 7a-i and 14a-f were evaluated for their antibacterial activity against a panel of MRSA strains by means of standard two-fold serial dilution method. Results: The majority of the synthesized moxifloxacin derivatives were active against most of the tested MRSA strains with MIC values in a range of 1 to 64 μg/mL. The mechanistic investigations revealed that topoisomerase IV was one of the targets for antibacterial activity. Conclusion: These derivatives are useful scaffolds for the development of novel topoisomerase IV inhibitors.

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Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

Molecules ◽

10.3390/molecules26010170 ◽

2020 ◽

Vol 26 (1) ◽

pp. 170

Author(s):

Urszula Kosikowska ◽

Monika Wujec ◽

Nazar Trotsko ◽

Wojciech Płonka ◽

Piotr Paneth ◽

...

Keyword(s):

Antibacterial Activity ◽

Methicillin Resistant Staphylococcus Aureus ◽

Resistant Bacteria ◽

Binding Affinities ◽

Substitution Pattern ◽

Minimal Inhibitory Concentrations ◽

Gram Positive Bacteria ◽

Structure Activity ◽

Drug Resistant Bacteria ◽

Reference Strains

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

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Novel Seleno- and Thio-Urea Containing Dihydropyrrol-2-One Analogues as Antibacterial Agents

Antibiotics ◽

10.3390/antibiotics10030321 ◽

2021 ◽

Vol 10 (3) ◽

pp. 321

Author(s):

Shekh Sabir ◽

Tsz Tin Yu ◽

Rajesh Kuppusamy ◽

Basmah Almohaywi ◽

George Iskander ◽

...

Keyword(s):

Antibacterial Activity ◽

Antibiotic Resistance ◽

Quorum Sensing ◽

Antibacterial Agents ◽

Inhibitory Concentration ◽

Resistant Bacteria ◽

Drug Resistant ◽

Positive Bacterium ◽

Quorum Sensing Inhibition ◽

Drug Resistant Bacteria

The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.

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Synergistic Antibacterial Activity of Lantana camara L., Parthenium hysterophorus L., Cannabis sativa L. and Justicia adhatoda L. Leaves Extract against Procured Multi-drug Resistant Bacteria In Vitro

European Journal of Medicinal Plants ◽

10.9734/ejmp/2021/v32i330379 ◽

2021 ◽

pp. 34-40

Author(s):

Jyoti Chandola ◽

Pooja Singh ◽

Rishabh Garg ◽

Narotam Sharma

Keyword(s):

Antibacterial Activity ◽

Medicinal Plants ◽

Cannabis Sativa ◽

Lantana Camara ◽

Parthenium Hysterophorus ◽

Resistant Bacteria ◽

Drug Resistant ◽

Drug Resistant Bacteria ◽

Weed Plants ◽

Justicia Adhatoda

The scientific study of this research has been focused on synergistic antibacterial activity of two weed plants, Lantana camara L., Parthenium hysterophorus L. alongwith two medicinal plants, Cannabis sativa L., Justicia adhatoda L. against multi- drug resistant (MDR) bacteria. Dried leaf powders of the plants were extracted using air-dried method followed by the ethanol- solvent extraction method for the crude extract of the leaves. The crude extracts were tested for antibacterial activity against three MDR bacteria, that is, one Gram positive bacteria- Staphylococcus aureus and two Gram negative bacteria- Escherichia coli and Proteus mirabilis. Out of 18 antibiotics tested against procured bacteria, Staphylococcus aureus was resistant to 10 out of 10 tested antibiotics, Escherichia coli was resistant to 4 out of 12 tested antibiotics and Proteus mirabilis was resistant to 9 out of 10 tested antibiotics. The tested weed plants and the medicinal plants when combined together showed more zone of inhibition against multidrug resistant bacteria ( Two combinations of phytochemicals Lantana camara, Cannabis sativa and Lantana camara, Cannabis sativa, Justicia adhatoda, Parthenium hysterophorus showed maximum zones of inhibition, that is, 30 mm) as compared to when these plants were tested solitarily, showing pronounced antibacterial activity. These findings showed that the antibacterial activity enhanced when they were combined together and this potential could be used against various infectious diseases with more research and modification in this area. Weed plants also holds as much importance as the medicinal plants although not to that extent, but they clearly inhibit the growth of bacteria and this property of weeds along with the medicinal plants holds a promising future in treating many diseases caused by multi-drug resistant bacteria on the pharmaceutical level.

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Quorum Sensing Inhibition in Chromobacterium violaceum, Antibacterial Activity and GC-MS Analysis of Centaurea praecox (Oliv. & Hiern) Extracts

Letters in Applied NanoBioScience ◽

10.33263/lianbs94.15691577 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1569-1577

Keyword(s):

Antibacterial Activity ◽

Quorum Sensing ◽

Research Strategy ◽

Chromobacterium Violaceum ◽

Resistant Bacteria ◽

Drug Resistant ◽

Control Drug ◽

Ms Analysis ◽

Drug Resistant Bacteria

The quorum sensing (QS) mechanism has become a viable research strategy for the discovery of plant-derived anti-virulent agents to control drug-resistant bacteria. The increasing incidences of drug-resistant bacteria and the effort to curb it necessitate this study. We investigated the QS inhibitory potential of Centaurea praecox extracts on Chromobacterium violaceum (CV), antibacterial activity, and determination of chemical composition using GC-MS. C. praecox was subjected to sequential extraction using hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), ethanol (ET), and aqueous (AQ) solvents. The extracts were subsequently evaluated for antibacterial activity using disc diffusion and QS violacein inhibition using spectrophotometry. The antibacterial effects of the extracts were moderate on gram-positive bacteria at 4 mg/mL in the order: HEX >EA >DCM >ET =AQ. However, the DCM extract demonstrated the most effective violacein inhibition of ≥80% at 0.3 mg/mL. QS violacein inhibitions were generally found to be concentration-dependent in the order: DCM >EA >HEX >ET =AQ with efficacies of ≥ 90% inhibition at ≥ 0.6 mg/mL. GC-MS analysis on the most potent DCM extract revealed N-vinylmethanimine, N-ethyl formamide, and propanamide among components identified. We concluded that C. praecox DCM extract contains bioactive chemicals as QS inhibitors and potential anti-virulent agents capable of combating the pathogenicity of drug-resistant bacteria in vivo.

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Antibacterial Effects of Oregano Essential Oil (OEO) and Its Potential Applications

Microbiology Research Journal International ◽

10.9734/mrji/2020/v30i430209 ◽

2020 ◽

pp. 19-25

Author(s):

R. Cabrera-Contreras ◽

R. Morelos-Ramírez ◽

J. P. Quiróz-Ríos ◽

D. Muñoz-Quiróz

Keyword(s):

Antibacterial Activity ◽

Essential Oil ◽

Essential Oils ◽

Staphylococcus Epidermidis ◽

Drug Resistant ◽

Human Pathogens ◽

Bacterial Strains ◽

Methicillin Resistant ◽

Reference Strains ◽

Serial Dilutions

Essential oils (EOs) are commonly used in food industry, due that they possess antioxidative and antimicrobial properties. There are few essential oils that have been used in medicine, due to its potent antibacterial activity against intrahospital pathogens. OEO has experimentally shown potent antibacterial effect on nosocomial Gram-positive bacteria, therefore it can be very useful in hospital environments, where there are many bacterial pathogens, which are the etiological agents of nosocomial infections and most of them are resistant to several antibiotics. Objective: The aim of this study was to determine antimicrobial effect of OEO on most frequent bacterial intrahospital pathogens: MRSA, MRSE comparatively to selected ATCC bacterial reference strains. Methods: This experimental study investigates the antibacterial action of oregano (Origanum vulgare) essential oil (OvEO) on two human pathogens: Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) Here, we used OEO against one of the most prominent antibiotic-resistant bacterial strains: methicillin-resistant SA (MRSAmecA+ = Meticillin Resistant SA and mecA- = Meticillin Resistance SA ), methicillin-resistant SE (MRSEmecA+ = Meticillin Resistance Staphylococcus epidermidis mecA+) and reference strains: S. aureus ATCC 700699, S. epidermidis ATCC 359845 and E. coli ATCC 25922. Bactericidal effects of the OEO on these bacteria were mainly evaluated using undiluted and four serial dilutions in coconut oil (CCO) l: 1:10, 1:100, 1:200, 1:400. Results: OEO, undiluted and 4 serial dilutions showed potent antibacterial activity against all strains tested. In conclusion, this OEO could be used as an alternative in medicine. The ability of OEO to inhibit and kill clinical Multi-Drug-Resistant (MDR): MRSA and MRSE strains, highlights it´s potential for use in the management of drug-resistant MDR infections in hospitals wards.

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Vacancy‐Induced Antibacterial Activity of XS 2– y Quantum Dots against Drug‐Resistant Bacteria for Treatment of Bacterial Keratitis

Small ◽

10.1002/smll.202004677 ◽

2020 ◽

Vol 16 (42) ◽

pp. 2004677

Author(s):

Huiyuan Li ◽

Xiao Wang ◽

Xiaofei Zhao ◽

Guanhua Li ◽

Fengyan Pei ◽

...

Keyword(s):

Quantum Dots ◽

Antibacterial Activity ◽

Resistant Bacteria ◽

Bacterial Keratitis ◽

Drug Resistant ◽

Drug Resistant Bacteria

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DNA Binding Ligands Targeting Drug-Resistant Bacteria: Structure, Activity, and Pharmacology

Journal of Medicinal Chemistry ◽

10.1021/jm030097a ◽

2003 ◽

Vol 46 (18) ◽

pp. 3914-3929 ◽

Cited By ~ 49

Author(s):

Jacob A. Kaizerman ◽

Matthew I. Gross ◽

Yigong Ge ◽

Sarah White ◽

Wenhao Hu ◽

...

Keyword(s):

Dna Binding ◽

Resistant Bacteria ◽

Drug Resistant ◽

Structure Activity ◽

Drug Resistant Bacteria

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Recombinant HNP-1 Produced by Escherichia coli Triggers Bacterial Apoptosis and Exhibits Antibacterial Activity against Drug-Resistant Bacteria

Microbiology Spectrum ◽

10.1128/spectrum.00860-21 ◽

2022 ◽

Author(s):

Qi Xie ◽

Yin Wang ◽

Mengmeng Zhang ◽

Shujia Wu ◽

Wei Wei ◽

...

Keyword(s):

Escherichia Coli ◽

Antibacterial Activity ◽

Mass Production ◽

Recombinant Protein Expression ◽

Cost Effective ◽

Resistant Bacteria ◽

Drug Resistant ◽

Effective Solution ◽

Drug Resistant Bacteria ◽

Human Neutrophil Peptide

Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical application has been hampered by the difficulty of mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that recombinant protein expression combined with ultrafiltration may be a simple and cost-effective solution to HNP-1 production.

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Antibacterial Activity of Guyabano, Ulasimang Bato, Sambong, and Tsaang Gubat Leaf Extracts against Common Drug-resistant Bacteria

Acta Medica Philippina ◽

10.47895/amp.v54i1.1087 ◽

2020 ◽

Vol 54 (1) ◽

Author(s):

Cecilia C. Maramba-Lazarte ◽

Lolita L. Cavinta ◽

Ma. Carmelita L. Sara

Keyword(s):

Antibacterial Activity ◽

Leaf Extract ◽

Resistant Bacteria ◽

Dilution Method ◽

Agar Dilution Method ◽

Moderate Activity ◽

Alcoholic Extract ◽

Drug Resistant ◽

Leaf Extracts ◽

E Coli

Background. Using plants as antimicrobials has long been a practice of traditional healers and validating these customs may lead to the discovery and development of useful herbal medicines. Objective. This study aimed to determine the antibacterial activity of guyabano, tsaang gubat, sambong, and ulasimang bato against common pathogens. Methods. Aqueous or alcoholic leaf extracts of the different medicinal plants were prepared. The solid agar dilution method was used to determine the MIC of guyabano, tsaang gubat, sambong, and ulasimang bato against common pathogens including Staphylococcus aureus, Echerichia coli, Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa, Salmonella typhi, and Shigella flexneri. Results. The alcoholic leaf extract of guyabano showed moderate activity against oxacillin-sensitive S. aureus with an MIC of 5-6.3 mg/mL. However, tsaang gubat did not exhibit any antibacterial activity for drug-resistant enteric organisms (S. typhi, S. flexneri, and E. coli) and S. aureus at a concentration of 25 mg/mL. Even at a concentration of 100mg/mL, ulasimang bato failed to show any antibacterial activity against drug-resistant S. aureus, S. pneumonia, H. influenzae, E. coli, and P. aeruginosa. Sambong alcoholic extract had some antibacterial activity against penicillin-resistant S. pneumoniae with an MIC of 12.5 mg/mL. Conclusions. Guyabano alcoholic leaf extract showed moderate antibacterial activity against oxacillin-sensitive S. aureus. Sambong alcoholic extract likewise exhibited inhibitory activity against S. pneumoniae. However, tsaang gubat and ulasimang bato aqueous extracts failed to show significant antibacterial activity for the pathogens tested.

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