Inhibition of biofilm formation by conformationally constrained indole-based analogues of the marine alkaloid oroidin

• Published in: Bioorganic & medicinal chemistry letters 2014-06, Vol.24 (11), p.2530-2534
• Main Authors: Hodnik, Žiga, Łoś, Joanna M., Žula, Aleš, Zidar, Nace, Jakopin, Žiga, Łoś, Marcin, Sollner Dolenc, Marija, Ilaš, Janez, Węgrzyn, Grzegorz, Peterlin Mašič, Lucija, Kikelj, Danijel
• Format: Article
• Language: English
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Biofilm; Biofilms - drug effects; Dose-Response Relationship, Drug; Indole; Indoles - chemistry; Inhibition; Marine; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Molecular Structure; Oroidin; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Staphylococcus aureus; Streptococcus mutans; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.03.094

Herein, we describe indole-based analogues of oroidin as a novel class of 2-aminoimidazole-based inhibitors of methicillin-resistant Staphylococcus aureus biofilm formation and, to the best of our knowledge, the first reported 2-aminoimidazole-based inhibitors of Streptococcus mutans biofilm formation. This study highlighted the indole moiety as a dibromopyrrole mimetic for obtaining inhibitors of S. aureus and S. mutans biofilm formation. The most potent compound in the series, 5-(trifluoromethoxy)indole-based analogue 4b (MBIC50=20μM), emerged as a promising hit for further optimisation of novel inhibitors of S. aureus and S. mutans biofilms.