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Extensive Structure-Activity Relationship Study of Albicidin's C-Terminal Dipeptidic p-Aminobenzoic Acid Moiety.

ABSTRACT: Albicidin is a recently described natural product that strongly inhibits bacterial DNA gyrase. The pronounced activity, particularly against Gram-negative bacteria, turns it into a promising lead structure for an antibacterial drug. Hence, structure-activity relationship studies are key for the in-depth understanding of structural features/moieties affecting gyrase inhibition, antibacterial activity and overcoming resistance. The 27 newly synthesized albicidins give profound insights into possibilities for variations of the C-terminus. Furthermore, in the present study, a novel derivative has been identified as overcoming resistance posed by the Klebsiella-protease AlbD. Structural modifications include, for example, azahistidine replacing the previous instable cyanoalanine as the central amino acid, as well as a triazole amide bond isostere between building blocks D and E.

SUBMITTER: Behroz I

PROVIDER: S-EPMC6972991 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Synthesis, crystal structure and biological activity of 2-hydroxyethylammonium salt of p-aminobenzoic acid.

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