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
  • Heterocyclic Compounds, 1-Ring/chemical synthesis
  • Heterocyclic Compounds, 1-Ring/chemistry
  • Heterocyclic Compounds, 1-Ring/pharmacology*
  • Solubility
  • Metals, Heavy/chemistry
  • Drug Resistance, Bacterial
  • Mycobacterium marinum/drug effects
  • Tuberculosis/drug therapy
  • Animals
  • Coordination Complexes/chemical synthesis
  • Coordination Complexes/chemistry
  • Coordination Complexes/pharmacology
  • Structure-Activity Relationship
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Bacterial Load/drug effects
  • Macrocyclic Compounds/chemical synthesis
  • Macrocyclic Compounds/chemistry
  • Macrocyclic Compounds/pharmacology*
  • Aza Compounds/chemical synthesis
  • Aza Compounds/chemistry
  • Aza Compounds/pharmacology*
  • Antitubercular Agents/chemical synthesis
  • Antitubercular Agents/chemistry
  • Antitubercular Agents/pharmacology*
  • Zebrafish
PubMed
29558124 Full text @ J. Med. Chem.
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping