Novel Small-Molecule Hybrid-Antibacterial Agents against S. aureus and MRSA Strains |
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| Authors: | Robin Gehrmann Tobias Hertlein Elisa Hopke Knut Ohlsen Michael Lalk Andreas Hilgeroth |
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| Institution: | 1.Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany;2.Institute of Molecular Infection Biology, Julius Maximilians University Wuerzburg, 97080 Wuerzburg, Germany; (T.H.); (E.H.); (K.O.);3.Institute of Biochemistry, Ernst Moritz Arndt University Greifswald, 17489 Greifswald, Germany; |
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| Abstract: | Ongoing resistance developments against antibiotics that also affect last-resort antibiotics require novel antibacterial compounds. Strategies to discover such novel structures have been dimerization or hybridization of known antibacterial agents. We found novel antibacterial agents by dimerization of indols and hybridization with carbazoles. They were obtained in a simple one-pot reaction as bisindole tetrahydrocarbazoles. Further oxidation led to bisindole carbazoles with varied substitutions of both the indole and the carbazole scaffold. Both the tetrahydrocarbazoles and the carbazoles have been evaluated in various S. aureus strains, including MRSA strains. Those 5-cyano substituted derivatives showed best activities as determined by MIC values. The tetrahydrocarbazoles partly exceed the activity of the carbazole compounds and thus the activity of the used standard antibiotics. Thus, promising lead compounds could be identified for further studies. |
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| Keywords: | antibacterial activity synthesis substituent structure– activity inhibition |
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