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Assessment of the rules related to gaining activity against Gram-negative bacteria.
Ropponen, Henni-Karoliina Diamanti, Eleonora Siemens, Alexandra Illarionov, Boris Haupenthal, Jörg Fischer, Markus Rottmann, Matthias Witschel, Matthias Hirsch, Anna K H
Ropponen, Henni-Karoliina
Diamanti, Eleonora
Siemens, Alexandra
Illarionov, Boris
Haupenthal, Jörg
Fischer, Markus
Rottmann, Matthias
Witschel, Matthias
Hirsch, Anna K H
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2021-03-03
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Abstract
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 Escherichia coli wild-type K12, whereas more distinct activity differences were observed in E. coli mutant strains ΔtolC, D22, ΔacrB and BL21(DE3)omp8. A comparison of the activity results of the E. coli mutants with respect to the known rules related to enhanced activity against Gram-negative bacteria revealed that applicability of the rules is not always ensured. Out of the four amino acids used in this study, glycine derivatives showed highest antibacterial activity, although still suffering from efflux issues.
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RSC Med Chem. 2021 Mar 3;12(4):593-601. doi: 10.1039/d0md00409j.
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en
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2632-8682
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Attribution 4.0 International