PUBLICATION
Development of acridine derivatives as selective Mycobacterium tuberculosis DNA gyrase inhibitors
- Authors
- Medapi, B., Meda, N., Kulkarni, P., Yogeeswari, P., Sriram, D.
- ID
- ZDB-PUB-170214-47
- Date
- 2016
- Source
- Bioorganic & Medicinal Chemistry 24: 877-85 (Journal)
- Registered Authors
- Kulkarni, Pushkar
- Keywords
- Acridine derivatives, DNA gyrase, Tuberculosis
- MeSH Terms
-
- Acridines/chemical synthesis*
- Acridines/pharmacology
- Animals
- Antitubercular Agents/chemical synthesis*
- Antitubercular Agents/pharmacology
- Bacterial Proteins/antagonists & inhibitors*
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism
- Cell Line
- Cell Survival/drug effects
- Chlorobenzoates/chemistry
- DNA Gyrase/genetics
- DNA Gyrase/metabolism*
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/physiology
- Ether-A-Go-Go Potassium Channels/antagonists & inhibitors
- Ether-A-Go-Go Potassium Channels/genetics
- Ether-A-Go-Go Potassium Channels/metabolism
- Gene Expression
- Heart Rate/drug effects
- Macrophages/cytology
- Macrophages/drug effects
- Macrophages/metabolism
- Mice
- Microbial Sensitivity Tests
- Mycobacterium tuberculosis
- Piperidines/chemical synthesis*
- Piperidines/pharmacology
- Quinolines/chemical synthesis*
- Quinolines/pharmacology
- Structure-Activity Relationship
- Topoisomerase II Inhibitors/chemical synthesis*
- Topoisomerase II Inhibitors/pharmacology
- Zebrafish
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 26787274 Full text @ Bioorg. Med. Chem.
Citation
Medapi, B., Meda, N., Kulkarni, P., Yogeeswari, P., Sriram, D. (2016) Development of acridine derivatives as selective Mycobacterium tuberculosis DNA gyrase inhibitors. Bioorganic & Medicinal Chemistry. 24:877-85.
Abstract
In this study we have designed p-phenylene diamine linked acridine derivative from our earlier reported quinoline-aminopiperidine hybrid MTB DNA gyrase inhibitors with aiming more potency and less cardiotoxicity. We synthesized thirty six compounds using four step synthesis from 2-chloro benzoic acid. Among them compound 4-chloro-N-(4-((2-methylacridin-9-yl)amino)phenyl)benzenesulphonamide (6) was found to be more potent with MTB DNA gyrase super coiling IC50 of 5.21±0.51μM; MTB MIC of 6.59μM and no zHERG cardiotoxicity at 30μM and 11.78% inhibition at 50μM against mouse macrophage cell line RAW 264.7.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping