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

2003 ◽  
Vol 46 (18) ◽  
pp. 3914-3929 ◽  
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

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

2021 ◽  
Vol 21 ◽  
Author(s):  
Rongxing Chen ◽  
Huarui Xue ◽  
Yazhou Xu ◽  
Tianwei Ma ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Topoisomerase Iv ◽  
Methicillin Resistant ◽  
Structure Activity ◽  
Drug Resistant Bacteria ◽  
Mrsa Strains

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.

scholarly journals Rapid profiling of drug-resistant bacteria using DNA-binding dyes and a nanopore-based DNA sequencer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ayumu Ohno ◽  
Kazuo Umezawa ◽  
Satomi Asai ◽  
Kirill Kryukov ◽  
So Nakagawa ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
16S Rrna ◽  
Clinical Samples ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Propidium Monoazide ◽  
Drug Resistant Bacteria ◽  
Metagenome Sequencing ◽  
Bacterial Mixtures

AbstractSpread of drug-resistant bacteria is a serious problem worldwide. We thus designed a new sequence-based protocol that can quickly identify bacterial compositions of clinical samples and their drug-resistance profiles simultaneously. Here we utilized propidium monoazide (PMA) that prohibits DNA amplifications from dead bacteria, and subjected the original and antibiotics-treated samples to 16S rRNA metagenome sequencing. We tested our protocol on bacterial mixtures, and observed that sequencing reads derived from drug-resistant bacteria were significantly increased compared with those from drug-sensitive bacteria when samples were treated by antibiotics. Our protocol is scalable and will be useful for quickly profiling drug-resistant bacteria.

scholarly journals Rapid profiling of drug-resistant bacteria using DNA-binding dyes and a nanopore-based DNA sequencer

2020 ◽  
Author(s):  
Ayumu Ohno ◽  
Kazuo Umezawa ◽  
Satomi Asai ◽  
Kirill Kryukov ◽  
So Nakagawa ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
16S Rrna ◽  
Clinical Samples ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Propidium Monoazide ◽  
Drug Resistant Bacteria ◽  
Metagenome Sequencing ◽  
Bacterial Mixtures

AbstractSpread of drug-resistant bacteria is a serious problem worldwide. We thus designed a new sequence-based protocol that can quickly identify bacterial compositions of clinical samples and their drug-resistance profiles simultaneously. Here we utilized propidium monoazide (PMA) that prohibits DNA amplifications from dead bacteria, and subjected the original and antibiotics-treated samples to 16S rRNA metagenome sequencing. We tested our protocol on bacterial mixtures, and observed that sequencing reads derived from drug-resistant bacteria were significantly increased compared with those from drug-sensitive bacteria when samples were treated by antibiotics. Our protocol is scalable and will be useful for quickly profiling drug-resistant bacteria.

Novel Antibiotics from Marine Sources

2011 ◽  
Vol 4 (3) ◽  
pp. 1446-1461 ◽  
Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag
Keyword(s):  
Pharmaceutical Industry ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Terrestrial Life ◽  
New Antibiotics ◽  
Antibiotic Compounds ◽  
New Generation ◽  
Novel Antibiotics ◽  
Untapped Resource

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.

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