Assessment of the structure-activity relationship of analogs of the <i>Naegleria fowleri</i> enolase inhibitor HEX.

ABSTRACT: The pathogenic free-living amoeba Naegleria fowleri causes primary amoebic meningoencephalitis (PAM), a highly fatal disease with limited treatment options, underscoring the urgent need for new therapeutics. Our previous studies identified (1-hydroxy-2-oxopiperidin-3-yl)phosphonic acid (HEX), an inhibitor of human enolase 2 (ENO2) involved in glucose metabolism, as a potent inhibitor of N. fowleri enolase (NfENO) with potent amoebicidal activity. In this study, we explored the structure-activity relationship (SAR) of HEX by modifying its hydroxamate and phosphonate functional groups, as well as introducing steric alterations to generate new analogs. Functional assays and computational-assisted SAR analysis provided insights into the impact of HEX modifications on N.

SUBMITTER: Kwain S 

PROVIDER: S-EPMC12186339 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature