A. Hilgeroth*, K. Yasrebi, S. Suzen, T. Hertlein, K. Ohlsen and M. Lalk
Background: Due to emerging resistances against antibiotics there is a strong need to find novel antibacterial agents with a novel structure to prevent early resistance developments.
Objective: Bisindole compounds with antibacterial activities which formally result from the reaction of an aldehyde with indole motivated to investigate the reaction of a dialdehyde and indole to give novel structures with potential antibacterial activities.
Method: Compounds were yielded by chemical synthesis and purified using column chromatography. The antibacterial activity was determined as minimal inhibitory growth activity in cultures of Gram-positive strains of Staphylococcus aureus and Enterococcus species.
Results: Cyclohepta[2,3-b]indoles have been yielded in a one-step reaction procedure with indole substitutions at the cycloheptane central core matching a solution for achieving fused novel cycloalkane indoles with functionalized residues of promising biological activity. So far fused cycloalkane indoles have not been available in a one-step procedure and moreover core functionalizations have been additional challenges. Various indole substitutions have been done to provide a first set of compounds.
Conclusion: Substituent-dependent effects have been suggested to influence the antibacterial activity and first compounds were identified with specific Staphylococcus activities and Enterococcus species effects towards Enterococcus faecalis as critical pathogens in hospital with upcoming resistances against standard antibiotics.
one-step procedure, fused indole, structure-activity relationships, antibacterial
Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Pharmaceutical Chemistry Department Tandogan, Ankara University, 06100 Ankara, Institute of Molecular Infection Biology, Julius-Maximilians-University Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzbug, Institute of Molecular Infection Biology, Julius-Maximilians-University Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzbug, Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald, Felix-Hausdorff-Str. 4, 17487 Greifswald