Insights into the antibacterial activity of cyclam derivatives

Cyclam is a tetraazamacrocycle with applications in diverse fields of medicine. In particular, the bis-cyclam derivative AMD3100 was found to be a highly active and selective HIV inhibitor by interaction with the viral CXCR4 receptor. More recently, cyclam derivatives and their metal complexes revealed anticancer, antimalarial, antischistosomal and antimicrobial properties. The trans-disubstituted cyclam salt [H₄{H₂(^4-CF3PhCH₂)₂Cyclam}]Cl₄ revealed to be highly active against Escherichia coli and Staphylococcus aureus. However, the molecular interactions between cyclams and bacteria remains unknown until now. In this context, the cyclam-based Cu(II) complex [{H₂(^4-CF3PhCH₂)₂Cyclam}Cu(H₂O)₂](CH₃COO)₂ was synthesized, characterized, and used to gain insights into the cyclams' mechanism of action in bacteria. Carboxylic acid derivatized magnetic beads (Dynabeads Carboxylic Acid©) were chemically bonded to [{H₂(^4-CF3PhCH₂)₂Cyclam}Cu(H₂O)₂](CH₃COO)₂, to identify E. coli interacting proteins. The most recent results on the field will be presented and discussed.