Methyl propiolate and 3-butynone: Starting points for synthesis of amphiphilic 1,2,3-triazole peptidomimetics for antimicrobial evaluation

Abstract

A library of 29 small 1,4-substituted 1,2,3-triazoles was prepared for studies of antimicrobial activity. The pharmacophore model investigated with these substrates was based on small peptidomimetics of antimicrobial peptides and antimicrobials isolated from marine organisms from sub-arctic regions. Using methyl 1,2,3-triazole-carboxylates and 1,2,3-triazole methyl ketones prepared through "click" chemistry we were able to synthesize the different cationic amphiphiles through three steps or less. Several structural modifications to the lipopohilic side and hydrophilic sides of the amphiphiles were investigated and compared with regards to antimicrobial activity and cytotoxicity in particular. The most promising amphiphile 10f displayed minimum inhibitory concentrations (MICs) between 4-16µg/mL against Gram-positive Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalacticae, and Gram-negative Escherichia coli and Pseudomonas aeruginosa. The decent level of antimicrobial activity and biofilm inhibition, short synthesis, and accessible reagents, makes this type of amphiphilic mimics interesting leads for further development.

Ionic liquids for the green synthesis of 1,2,3-triazoles: a systematic review

“…35–42 In this review article, we summarize various reports available on synthesis of 1,2,3-triazoles utilizing ILs as a greener solvent or potential catalyst under thermal conditions or microwave irradiation. 1,2,3-Triazole is a significant scaffold with promising applications in different fields such as medicinal chemistry, 43–55 biochemistry, 56 dendrimers, 57–62 materials chemistry, 63–67 chemical sensing, 68–70 ionic recognition, 71,72 peptidomimetics, 73,74 and bioconjugation. 75 1,2,3-Triazoles came into the mainstream of synthesis after the great work by Huisgen in this field in 1960, who provided a more straightforward laboratory synthetic pathway for the synthesis of 1,2,3-triazoles that involves the 1,3-dipolar cycloaddition of terminal alkynes with organic azides under thermal conditions.…”

The Rationale and Evidence for Use of Inhaled Antibiotics to ControlPseudomonas aeruginosaInfection in Non-cystic Fibrosis Bronchiectasis

“…( 81 , 94–96 ) One of these alginate oligosaccharides (OligoG CF-5/20) was found to be safe for inhalation both in healthy and in chronically diseased lung patients and is currently undergoing phase IIb trials in CF patients. ( 97 ) Furthermore, a new family of compounds (“peptidomimetics”), mimicking antimicrobial peptides and showing activity against P. aeruginosa , ( 96 , 98 ) are currently being evaluated in preclinical studies. ( 95 , 96 )…”

Matrix isolation study of methyl propiolate in argon and nitrogen matrices

“…It has been used in the synthesis of different types of compounds via domino reactions, [8][9][10] as an intermediate in cycloadditions, [11,12] as a starting material for the production of substituted triazoles with antimicrobial activity. [13] MP has also been widely used in reactions with vinyl gold complexes, [14] bis-insertion reactions, [15] and free-radicals-related reactions. [16] Li and Brill [17] studied the hydrothermolysis of MP and investigated the relative rates for its three stages: decarboxylation, decarbonylation, and hydrolysis.…”