Antibacterial Activity of Metergoline Analogues: Revisiting the Ergot Alkaloid Scaffold for Antibiotic Discovery.

ABSTRACT: Metergoline is a semisynthetic ergot alkaloid identified recently as an inhibitor of the Gram-negative intracellular pathogen Salmonella Typhimurium (S. Tm). With the previously unknown antibacterial activity of metergoline, we explored structure-activity relationships (SARs) with a series of carbamate, urea, sulfonamide, amine, and amide analogues. Cinnamide and arylacrylamide derivatives show improved potency relative to metergoline against Gram-positive bacteria, and pyridine derivative 38 is also effective against methicillin-resistant Staphylococcus aureus (MRSA) in a murine skin infection model. Arylacrylamide analogues of metergoline show modest activity against wild-type (WT) Gram-negative bacteria but are more active against strains of efflux-deficient

SUBMITTER: Johnson JW 

PROVIDER: S-EPMC8842143 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature