Synthesis and antimicrobial evaluation of cationic low molecular weight amphipathic 1,2,3-triazoles

Thomas A Bakka; Morten B Strøm; Jeanette H Andersen; Odd R Gautun

doi:10.1016/j.bmcl.2017.01.092

Synthesis and antimicrobial evaluation of cationic low molecular weight amphipathic 1,2,3-triazoles

Bioorg Med Chem Lett. 2017 Mar 1;27(5):1119-1123. doi: 10.1016/j.bmcl.2017.01.092. Epub 2017 Feb 1.

Authors

Thomas A Bakka¹, Morten B Strøm², Jeanette H Andersen³, Odd R Gautun⁴

Affiliations

¹ Department of Chemistry, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway.
² Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, NO-9037 Tromsø, Norway.
³ Marbio, Faculty of Biosciences, Fisheries and Economics, University of Tromsø, NO-9037 Tromsø, Norway.
⁴ Department of Chemistry, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway. Electronic address: odd.r.gautun@ntnu.no.

PMID: 28189422
DOI: 10.1016/j.bmcl.2017.01.092

Abstract

A library of 28 small cationic 1,4-substituted 1,2,3-triazoles was prepared for studies of antimicrobial activity. The structures addressed the pharmacophore model of small antimicrobial peptides and an amphipathic motif found in marine antimicrobials. Eight compounds showed promising antimicrobial activity, of which the most potent compound 10b displayed minimum inhibitory concentrations of 4-8μg/mL against Streptococcus agalacticae, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis. The simple syntheses and low degree of functionalization make these 1,4-substituted 1,2,3-triazoles interesting for further optimizations.

Keywords: 1,2,3-Triazoles; Antibacterial; Click chemistry; Marine natural product mimics; Peptidomimetics.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Cations
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Microbial Sensitivity Tests
Molecular Weight
Triazoles / chemical synthesis*
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Anti-Bacterial Agents
Cations
Triazoles