Improved Antibacterial Activity of 1,3,4-Oxadiazole-Based Compounds That Restrict <i>Staphylococcus aureus</i> Growth Independent of LtaS Function.

ABSTRACT: The lipoteichoic acid (LTA) biosynthesis pathway has emerged as a promising antimicrobial therapeutic target. Previous studies identified the 1,3,4 oxadiazole compound 1771 as an LTA inhibitor with activity against Gram-positive pathogens. We have succeeded in making six 1771 derivatives and, through subsequent hit validation, identified the incorporation of a pentafluorosulfanyl substituent as central in enhancing activity. Our newly described derivative, compound 13, showed a 16- to 32-fold increase in activity compared to 1771 when tested against a cohort of multidrug-resistant Staphylococcus aureus strains while simultaneously exhibiting an improved toxicity profile against mammalian cells. Molecular techniques were employed in which the assumed target, lipoteichoic acid

SUBMITTER: Douglas EJA 

PROVIDER: S-EPMC10644342 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature