Back to Search
Start Over
Management of Neisseria gonorrhoeae infection: from drug resistance to drug repurposing.
- Source :
-
Expert opinion on therapeutic patents [Expert Opin Ther Pat] 2024 Jun; Vol. 34 (6), pp. 511-524. Date of Electronic Publication: 2024 Jun 14. - Publication Year :
- 2024
-
Abstract
- Introduction: Neisseria gonorrhoeae is a common sexually transmitted disease connected with extensive drug resistance to many antibiotics. Presently, only expanded spectrum cephalosporins (ceftriaxone and cefixime) and azithromycin remain useful for its management.<br />Areas Covered: New chemotypes for the classical antibiotic drug target gyrase/topoisomerase IV afforded inhibitors with potent binding to these enzymes, with an inhibition mechanism distinct from that of fluoroquinolones, and thus less prone to mutations. The α-carbonic anhydrase from the genome of this bacterium (NgCAα) was also validated as an antibacterial target.<br />Expert Opinion: By exploiting different subunits from the gyrase/topoisomerase IV as well as new chemotypes, two new antibiotics reached Phase II/III clinical trials, zoliflodacin and gepotidacin. They possess a novel inhibition mechanism, binding in distinct parts of the enzyme compared to the fluoroquinolones. Other chemotypes with inhibitory activity in these enzymes were also reported. NgCAα inhibitors belonging to a variety of classes were obtained, with several sulfonamides showing MIC values in the range of 0.25-4 µg/mL and significant activity in animal models of this infection. Acetazolamide and similar CA inhibitors might thus be repurposed as antiinfectives. The scientific/patent literature has been searched for on PubMed, ScienceDirect, Espacenet, and PatentGuru, from 2016 to 2024.
- Subjects :
- Humans
Animals
Topoisomerase II Inhibitors pharmacology
Oxazolidinones pharmacology
Microbial Sensitivity Tests
DNA Topoisomerase IV antagonists & inhibitors
DNA Topoisomerase IV metabolism
DNA Gyrase metabolism
Morpholines
Isoxazoles
Spiro Compounds
Heterocyclic Compounds, 3-Ring
Barbiturates
Acenaphthenes
Neisseria gonorrhoeae drug effects
Neisseria gonorrhoeae enzymology
Anti-Bacterial Agents pharmacology
Drug Repositioning
Patents as Topic
Gonorrhea drug therapy
Gonorrhea microbiology
Drug Resistance, Bacterial
Subjects
Details
- Language :
- English
- ISSN :
- 1744-7674
- Volume :
- 34
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Expert opinion on therapeutic patents
- Publication Type :
- Academic Journal
- Accession number :
- 38856987
- Full Text :
- https://doi.org/10.1080/13543776.2024.2367005