Synthesis and evaluation of antibacterial and trypanocidal activity of derivatives of monensin A. (15th February 2022)

• Record Type: Journal Article
• Authors: Jędrzejczyk, Marta; Stępczyńska, Natalia; Klejborowska, Greta; Podsiad, Małgorzata; Stefańska, Joanna; Steverding, Dietmar; Huczyński, Adam
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 58(2022)
• Publication Date: 2022-02-15
• Subjects: Antimicrobial activity -- Antiparasitic activity -- Natural products -- Polyether ionophores; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128521
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The synthesis and biological evaluation of eleven derivatives of the natural polyether ionophore monensin A (MON ), modified at the C-26 position, is presented. Eight urethane and three ester derivatives were tested for their antimicrobial activity against different strains of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa . In addition, their antiparasitic activity was also evaluated with bloodstream forms of Trypanosoma brucei . The majority of the modified ionophores were active against a variety of Gram-positive bacterial strains, including methicillin-resistant S. epidermidis, and showed better antibacterial activity than the unmodified MON . The phenyl urethane derivative of MON exhibited the most promising antibacterial activity of all tested compounds, with minimal inhibitory concentration values of 0.25–0.50 μg/ml. In contrast, none of the MON derivatives displayed higher antitrypanosomal activity than the unmodified ionophore.