biostudies-literatureUnknown13Hamad MThe serious challenge posed by multidrug-resistant bacterial infections with concomitant treatment failure and high mortality rates presents an urgent threat to the global health. We herein report the discovery of a new class of potent antimicrobial compounds that are highly effective against Gram-positive bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). The compounds were efficiently synthesized in one-pot employing a cascade of Groebke-Blackburn-Bienaymé and aza-Michael addition reactions. Phenotypic screening of the pilot library against various bacterial species including methicillin-sensitive and MRSA strains, has identified potent chemotypes with minimal inhibitory concentrations (MIC) of 3.125-6.25 μg/ml. The most potent compounds were fast-acting at erFrontiers in microbiology823394https://www.ebi.ac.uk/biostudies/studies/S-EPMC8846302biostudies-literatureAntibacterial Activity of Small Molecules Which Eradicate Methicillin-Resistant <i>Staphylococcus aureus</i> Persisters.PMC8846302Hamad MAl-Tel THAl-Marzooq FSulaiman AZaher DMSrinivasulu VOmar HAOrive GfalseAntibacterial Activity of Small Molecules Which Eradicate Methicillin-Resistant <i>Staphylococcus aureus</i> Persisters.The serious challenge posed by multidrug-resistant bacterial infections with concomitant treatment failure and high mortality rates presents an urgent threat to the global health. We herein report the discovery of a new class of potent antimicrobial compounds that are highly effective against Gram-positive bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). The compounds were efficiently synthesized in one-pot employing a cascade of Groebke-Blackburn-Bienaymé and aza-Michael addition reactions. Phenotypic screening of the pilot library against various bacterial species including methicillin-sensitive and MRSA strains, has identified potent chemotypes with minimal inhibitory concentrations (MIC) of 3.125-6.25 μg/ml. The most potent compounds were fast-acting at er2022-01-01T00:00:00Z20222025-04-26T12:19:27.603Z2025-04-06T13:55:31.333ZS-EPMC88463023517804310.3389/fmicb.2022.823394