Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1 H -imidazol-5-yl-1 H -indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus

• Published in: Antibiotics (Basel) 2022-10, Vol.11 (10)
• Main Authors: Li, Steven A, Zheng, Rebecca J, Sue, Kenneth, Bourguet-Kondracki, Marie-Lise, Troudi, Azza, Brunel, Jean Michel, Copp, Brent R, Cadelis, Melissa M
• Format: Article
• Language: English
• ISSN: 2079-6382; 2079-6382

Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant bacteria resulting in a desperate need for antibiotics with new mechanisms of action. As part of our search for new antimicrobials we have screened an in-house library of compounds and identified two 3-substituted-1 -imidazol-5-yl-1 -indoles as weak growth inhibitors (MIC 16 µg/mL) against methicillin-resistant (MRSA). An extensive library of analogues was prepared using the Van Leusen three-component reaction, biological evaluation of which led to the identification of two analogues ( and ) with favorable anti-MRSA activity (MIC ≤ 0.25 µg/mL) which also lacked cytotoxic or hemolytic properties. The screening campaign also identified two derivatives, a phenethyl-indole-imidazole and a 5-phenyl-1 -imidazole that were non-toxic selective antifungals towards . These results have identified 3-substituted-1 -imidazol-5-yl-1 -indoles and 5-phenyl-1 -imidazoles as new structural scaffolds for further investigation as anti-MRSA and anti- agents, respectively.