biostudies-literatureRopponen HKHelmholtz AssociationVerband der Chemischen Industrie593-601https://www.ebi.ac.uk/biostudies/studies/S-EPMC8128065biostudies-literatureUnknown12(4)In the search for new antibacterial compounds, we repositioned an antimalarial compound class by derivatising it based on the so-called "eNTRy" rules for enhanced accumulation into Gram-negative bacteria. We designed, synthesised and evaluated a small library of amino acid modified compounds together with the respective Boc-protected analogues, leading to no substantial improvement in antibacterial activity against <i>Escherichia coli</i> wild-type K12, whereas more distinct activity differences were observed in <i>E. coli</i> mutant strains Δ<i>tolC</i>, D22, Δ<i>acrB</i> and BL21(DE3)omp8. A comparison of the activity results of the <i>E. coli</i> mutants with respect to the known rules related to enhanced activity against Gram-negative bacteria revealed that applicability of the rules iRSC medicinal chemistryAssessment of the rules related to gaining activity against Gram-negative bacteria.PMC8128065Kekulé Mobility FellowshipInitiative and Networking FundHirsch AKHRopponen HKRottmann MFischer MIllarionov BHaupenthal JSiemens AWitschel MDiamanti EfalseAssessment of the rules related to gaining activity against Gram-negative bacteria.In the search for new antibacterial compounds, we repositioned an antimalarial compound class by derivatising it based on the so-called "eNTRy" rules for enhanced accumulation into Gram-negative bacteria. We designed, synthesised and evaluated a small library of amino acid modified compounds together with the respective Boc-protected analogues, leading to no substantial improvement in antibacterial activity against <i>Escherichia coli</i> wild-type K12, whereas more distinct activity differences were observed in <i>E. coli</i> mutant strains Δ<i>tolC</i>, D22, Δ<i>acrB</i> and BL21(DE3)omp8. A comparison of the activity results of the <i>E. coli</i> mutants with respect to the known rules related to enhanced activity against Gram-negative bacteria revealed that applicability of the rules i2021-01-01T00:00:00Z2021 Apr2025-05-29T21:23:42.124Z2025-05-29T21:23:42.124ZS-EPMC81280653404663010.1039/d0md00409j