Positive Charge in an Antimalarial Compound Unlocks Broad-Spectrum Antibacterial Activity.

ABSTRACT: In this study, we synthesized a library of eNTRy-rule-compliant compounds by introducing ionizable nitrogen atoms to an antimalarial compound. These positively charged derivatives gained activity against both Gram-negative and -positive bacteria, Mycobacterium tuberculosis, and boosted Plasmodium falciparum inhibition to the double-digit nanomolar range. Overcoming and remaining inside the cell envelope of Gram-negative bacteria (GNB) is one of the major difficulties in antibacterial drug discovery and development. The eNTRy rules (N = ionizable nitrogen, T = low three-dimensionality, R = rigidity) can be a useful structural guideline to improve accumulation of small molecules in GNB. With the aim of unlocking Gram-negative activity, we added amines and (cyclic) N-alky

SUBMITTER: Braun-Cornejo M 

PROVIDER: S-EPMC11938010 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature