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Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action
- Source :
- Bioorganic & Medicinal Chemistry. 27:1274-1282
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Filamenting temperature-sensitive mutant Z (FtsZ) is recognized as a promising target for new antibiotics development because of its high conservatism and pivotal role in the bacteria cell division. The aromatic heterocyclic scaffold of indole is known showing merit medical functions in antiviral and antimicrobial. In the present study, a series of 1-methylquinolinium derivatives, which were integrated with an indole fragment at its 2-position and a variety of amino groups (cyclic or linear, mono- or di-amine) at the 4-position were synthesized and their antibacterial activities were evaluated. The results of antibacterial study show that the representative compounds can effectively inhibit the growth of testing strains including MRSA and VRE, with MIC values of 1–4 μg/mL by bactericidal mode. The mode of action assays revealed that c2 can effectively disrupt the rate of GTP hydrolysis and dynamic polymerization of FtsZ, and thus inhibits bacterial cell division and then causes bacterial cell death. In addition, the result of resistance generation experiment reveals that c2 is not likely to induce resistance in S. aureus.
- Subjects :
- Indoles
medicine.drug_class
Clinical Biochemistry
Antibiotics
Mutant
Pharmaceutical Science
Microbial Sensitivity Tests
Gram-Positive Bacteria
01 natural sciences
Biochemistry
Bacterial cell structure
Structure-Activity Relationship
Drug Resistance, Bacterial
Gram-Negative Bacteria
Drug Discovery
medicine
FtsZ
Mode of action
Molecular Biology
Indole test
Dose-Response Relationship, Drug
Molecular Structure
biology
010405 organic chemistry
Chemistry
Quinolinium Compounds
Organic Chemistry
Antimicrobial
Anti-Bacterial Agents
0104 chemical sciences
010404 medicinal & biomolecular chemistry
biology.protein
Molecular Medicine
Antibacterial activity
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....3a044eda1d0c78be1fd157e33e772e53