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.
Highlights
Molecules 2022, 27, 61. https://Antibiotic resistance poses a threat to human health today [1]
It would be most favourable to find new compounds that are available without enormous costs for production or synthesis to become attractive for pharmaceutical companies
Novel bisindole carbazoles and tetrahydrocarbazoles were available in a simple one-pot reaction with a final aromatizing reaction step
Summary
Antibiotic resistance poses a threat to human health today [1]. It has been predicted that without urgent actions in 2050 10 million people a year will die from bacterial infections that cannot be treated due to antibiotic resistance [2,3]. It has to be stated that resistances have been described against these antibiotics of last-resort [6,7] New antibiotics, such as linezolid or daptomycin, were discovered up to the end of the last century, but as of today there is a lack of novel compounds [1,8]. One option to discover new potential antibiotic drugs is the dimerization or hybridization of known antibacterial structure elements [17,18]. Applying this strategy, enhanced antibacterial activities have been described for bisindole compounds compared to respective single indole derivatives [19,20]. We discovered first promising lead structures of the various synthesized compound classes
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