Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action
| Autor: | Ziwei Tang, Wing-Leung Wong, Qi Guo, Ning Sun, Wenchang Yuan, Xuan-He Huang, Yu Jing Lu, Zhiyuan Fang, Sen-Yuan Cai, Hai Lin, Ying Li, Kwok Yin Wong |
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| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Bioorganic & Medicinal Chemistry. 27:1274-1282 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2019.02.024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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