Microwave-assisted one-pot synthesis and anti-biofilm activity of 2-amino-1H-imidazole/triazole conjugates.
A microwave-assisted protocol was developed for the construction of 2-amino-1H-imidazole/triazole conjugates starting from the previously described 2-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-4-ium salts. The process involves a one-pot hydrazinolysis/Dimroth-rearrangement of these salts followed by a ligand-free copper nanoparticle-catalyzed azide-alkyne Huisgen cycloaddition. The 2-amino-1H-imidazole/triazole conjugates showed moderate to high preventive activity against biofilms of S. Typhimurium, E. coli, P. aeruginosa and S. aureus. The most active compounds had BIC50 values between 1.3 and 8 μM. A remarkable finding was that introduction of the triazole moiety into the side chain of 2-aminoimidazoles with a long (C8-C13) 2N-alkyl chain did drastically improve their activity. Conclusively, the 2-amino-1H-imidazole/triazole scaffold provides a lead structure for further design and development of novel biofilm inhibitors.
Centre of Microbial and Plant Genetics (CMPG), Department of Microbial and Molecular Systems, KU Leuven, Kasteelpark Arenberg 20, Box 2460, B-3001 Leuven, Belgium. Jozef.Vanderleyden@biw.kuleuven.be.
Hans
H
Steenackers
Denis
D
Ermolat'ev
Tran Thi Thu
TT
Trang
Bharat
B
Savalia
Upendra K
UK
Sharma
Ami
A
De Weerdt
Anamik
A
Shah
Jozef
J
Vanderleyden
Erik V
EV
Van der Eycken
D018441:Biofilms / Q000187:drug effects*; D002625:Chemistry, Organic / Q000379:methods*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008872:Microwaves; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000502:physiology; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D007093:Imidazoles; D014230:Triazoles; C014973:2-aminoimidazole