ZFIN ID: ZDB-PUB-180321-28
Anti-Tubercular bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and In Vivo Studies
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.
Date: 2018
Source: Journal of medicinal chemistry   61(8): 3595-3608 (Journal)
Registered Authors: Hortle, Elinor, Oehlers, Stefan
Keywords: none
MeSH Terms:
  • Animals
  • Antitubercular Agents/chemical synthesis
  • Antitubercular Agents/chemistry
  • Antitubercular Agents/pharmacology*
  • Aza Compounds/chemical synthesis
  • Aza Compounds/chemistry
  • Aza Compounds/pharmacology*
  • Bacterial Load/drug effects
  • Coordination Complexes/chemical synthesis
  • Coordination Complexes/chemistry
  • Coordination Complexes/pharmacology
  • Drug Resistance, Bacterial
  • Heterocyclic Compounds, 1-Ring/chemical synthesis
  • Heterocyclic Compounds, 1-Ring/chemistry
  • Heterocyclic Compounds, 1-Ring/pharmacology*
  • Macrocyclic Compounds/chemical synthesis
  • Macrocyclic Compounds/chemistry
  • Macrocyclic Compounds/pharmacology*
  • Metals, Heavy/chemistry
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium marinum/drug effects
  • Solubility
  • Structure-Activity Relationship
  • Tuberculosis/drug therapy
  • Zebrafish
PubMed: 29558124 Full text @ J. Med. Chem.
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.