Metergoline is a semisynthetic ergot alkaloid identified recently as an inhibitor of <i>Salmonella</i> Typhimurium, an intracellular Gram-negative pathogen. A series of carbamate, urea, sulfonamide, amine, and amide analogues of metergoline were synthesized and evaluated against Gram-positive and Gram-negative bacteria. Cinnamide and arylacrylamide analogues showed improved potency relative to metergoline, and one analogue was effective against MRSA in a murine skin infection model. Arylacrylamide derivatives were inactive against wild-type Gram-negative bacteria but their potencies were improved considerably (up to &gt;128-fold) in combination with outer-membrane permeabilizer SPR741. Metergoline analogues also retained activity against multidrug-resistant strains of <i>Staphylococcus aureus</i>, suggesting a mechanism of action that is distinct from clinically used antibiotic classes.

Antibacterial activity of metergoline analogues and investigations into their mechanisms of action

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.