Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action
A new series of indolyl-quinolinium derivatives perturb the polymerization of FtsZ with strong antibacterial activities. [Display omitted] •Novel indolyl-quinolinium derivatives were synthesized.•The antibacterial activity of quinolinium derivatives were evaluated.•c2 and c9 possess potent antibacte...
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Published in | Bioorganic & medicinal chemistry Vol. 27; no. 7; pp. 1274 - 1282 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
OXFORD
Elsevier Ltd
01.04.2019
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | A new series of indolyl-quinolinium derivatives perturb the polymerization of FtsZ with strong antibacterial activities.
[Display omitted]
•Novel indolyl-quinolinium derivatives were synthesized.•The antibacterial activity of quinolinium derivatives were evaluated.•c2 and c9 possess potent antibacterial activity against MRSA and VRE.•Biological assays suggest antibacterial activity of c2 may associated with FtsZ.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2019.02.024 |