Cyclam-based antibacterial molecules eradicate Gram-negative superbugs with potent efficacy against human corneal infection

Abstract

Cyclam-based antibacterial molecules (CAMs) that display potent activity against both the planktonic and stationary phase of multidrug-resistant Gram-negative bacteria were rationally designed.

Bacterial Nosocomial Infections: Multidrug Resistance as a Trigger for the Development of Novel Antimicrobials

“…Additionally, positive charge provided by the cationic amino acid residue di-amino butyric acid and a significant hydrophobicity due to the amino acids phenylalanine and leucine play an essential role in their effectiveness. Cyclam-based derivatives have been designed to mimic this class of antibiotics [ 128 ]. The cyclic molecular backbone was mimicked by the incorporation of cyclam, and the lipophilicity was promoted by conjugating different long-chain fatty acids.…”

“…Phenylalanine and leucine were also introduced in the structure. The results revealed that longer aliphatic chains led to an increase in the antibacterial activity against A. baumannii , P. aeruginosa , E. coli, and K. pneumoniae [ 128 ]. The most active compound showed a potent activity in the concentration range of 2–8 μg/mL to both wild-type and drug-resistant clinical isolates of those bacteria.…”

“…The compound was found to be also highly active against MRSA, with a MIC value of 2 μg/mL. The ex vivo antibacterial activity against P. aeruginosa ATCC 27853 and P. aeruginosa L-2026/17 portrayed its effectivity in the treatment of a human corneal infection model by reducing the bacterial burden by 1.5 log for P. aeruginosa ATCC 27853 and by 1.9 log for the drug-resistant clinical isolate obtained from an ocular infected eye [ 128 ].…”

Copper(ii) complexes of N-propargyl cyclam ligands reveal a range of coordination modes and colours, and unexpected reactivity

“…3 The resultant versatility has enabled the application of cyclam derivatives across a wide range of areas including chemosensing, 5,6 biomimicry, 7,8 molecular switches, 9,10 supramolecular systems, 11,12 catalysis, [13][14][15] and medicine. [16][17][18] Pendant groups including amine, alcohol, thiol, ester, carboxylic acid, amide, carbamate, urea, sulfonamide, nitrile, thioester, pyridyl, triazolyl and phosphonate functionality have been incorporated on side-arms of varying length and complexity, 2,3 to modulate properties such as chelate effects, the selectivity of metal ion-binding, side-chain reactivity, and pendant lability.…”

Copper(II) Complexes of N-Propargyl Cyclam Ligands Reveal a Range of Coordination Modes and Colours, and Unexpected Reactivity

“…3 The resultant versatility has enabled the application of cyclam derivatives across a wide range of areas including chemosensing, 5,6 biomimicry, 7,8 molecular switches, 9, 10 supramolecular systems, 11,12 catalysis, [13][14][15] and medicine. [16][17][18] Pendant groups including amine, alcohol, thiol, ester, carboxylic acid, amide, carbamate, urea, sulfonamide, nitrile, thioester, pyridyl, triazolyl and phosphonate functionality have been incorporated on side-arms of varying length and complexity, 2,3 to modulate properties such as chelate effects, the selectivity of metal ion-binding, side-chain reactivity, and pendant lability.…”