Abstract |
Antibiotics with good therapeutic value and novel mechanism of action are becoming increasingly important in today's battle against bacterial resistance. One of the popular targets being DNA gyrase, is currently becoming well-established and clinically validated for the development of novel antibacterials. In the present work, a series of forty eight quinoline-aminopiperidine based urea and thiourea derivatives were synthesized as pharmacophoric hybrids and evaluated for their biological activity. Compound, 1-(4-chlorophenyl)-3-(1-(6-methoxy-2-methylquinolin-4-yl)piperidin-4-yl)thiourea (45) was found to exhibit promising in vitro Mycobacterium smegmatis GyrB IC₅₀ of 0.95 ± 0.12 μM and a well correlated Mycobacterium tuberculosis (MTB) DNA gyrase supercoiling IC₅₀ of 0.62 ± 0.16 μM. Further, compound 45 also exhibited commendable MTB MIC, safe eukaryotic cytotoxic profile with no signs of cardiotoxicity in zebrafish ether-a-go-go-related gene (zERG).
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Authors | Brahmam Medapi, Janupally Renuka, Shalini Saxena, Jonnalagadda Padma Sridevi, Raghavender Medishetti, Pushkar Kulkarni, Perumal Yogeeswari, Dharmarajan Sriram |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 23
Issue 9
Pg. 2062-78
(May 01 2015)
ISSN: 1464-3391 [Electronic] England |
PMID | 25801151
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Anti-Bacterial Agents
- Piperidines
- Quinolines
- Topoisomerase II Inhibitors
- quinoline
- DNA Gyrase
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Topics |
- Animals
- Anti-Bacterial Agents
(chemical synthesis, chemistry, pharmacology)
- DNA Gyrase
(metabolism)
- Dose-Response Relationship, Drug
- Drug Design
- Microbial Sensitivity Tests
- Molecular Structure
- Mycobacterium smegmatis
(drug effects, enzymology)
- Mycobacterium tuberculosis
(drug effects, enzymology)
- Piperidines
(chemistry, pharmacology)
- Quinolines
(chemistry, pharmacology)
- Structure-Activity Relationship
- Topoisomerase II Inhibitors
(chemical synthesis, chemistry, pharmacology)
- Zebrafish
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