PUBLICATION
Anti-Tubercular bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and In Vivo Studies
- Authors
- Spain, M., Wong, J.K., Nagalingam, G., Batten, J.M., Hortle, E., Oehlers, S., Jiang, X.F., Murage, H.E., Orford, J.T., Crisologo, P., Triccas, J.A., Rutledge, P.J., Todd, M.H.
- ID
- ZDB-PUB-180321-28
- Date
- 2018
- Source
- Journal of medicinal chemistry 61(8): 3595-3608 (Journal)
- Registered Authors
- Hortle, Elinor, Oehlers, Stefan
- Keywords
- none
- MeSH Terms
-
- Tuberculosis/drug therapy
- Bacterial Load/drug effects
- Microbial Sensitivity Tests
- Drug Resistance, Bacterial
- Macrocyclic Compounds/chemical synthesis
- Macrocyclic Compounds/chemistry
- Macrocyclic Compounds/pharmacology*
- Animals
- Antitubercular Agents/chemical synthesis
- Antitubercular Agents/chemistry
- Antitubercular Agents/pharmacology*
- Metals, Heavy/chemistry
- Mycobacterium marinum/drug effects
- Zebrafish
- Coordination Complexes/chemical synthesis
- Coordination Complexes/chemistry
- Coordination Complexes/pharmacology
- Aza Compounds/chemical synthesis
- Aza Compounds/chemistry
- Aza Compounds/pharmacology*
- Structure-Activity Relationship
- Solubility
- Heterocyclic Compounds, 1-Ring/chemical synthesis
- Heterocyclic Compounds, 1-Ring/chemistry
- Heterocyclic Compounds, 1-Ring/pharmacology*
- Molecular Structure
- PubMed
- 29558124 Full text @ J. Med. Chem.
Citation
Spain, M., Wong, J.K., Nagalingam, G., Batten, J.M., Hortle, E., Oehlers, S., Jiang, X.F., Murage, H.E., Orford, J.T., Crisologo, P., Triccas, J.A., Rutledge, P.J., Todd, M.H. (2018) Anti-Tubercular bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and In Vivo Studies. Journal of medicinal chemistry. 61(8):3595-3608.
Abstract
We recently reported the discovery of non-toxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping