TY  - JOUR
A1  - Ashraf, Kerolos
A1  - Yasrebi, Kaveh
A1  - Hertlein, Tobias
A1  - Ohlsen, Knut
A1  - Lalk, Michael
A1  - Hilgeroth, Andreas
T1  - Novel effective small-molecule antibacterials against \(Enterococcus\) strains
JF  - Molecules
N2  - \(Enterococcus\) species cause increasing numbers of infections in hospitals. They contribute to the increasing mortality rates, mostly in patients with comorbidities, who suffer from severe diseases. \(Enterococcus\) resistances against most antibiotics have been described, including novel antibiotics. Therefore, there is an ongoing demand for novel types of antibiotics that may overcome bacterial resistances. We discovered a novel class of antibiotics resulting from a simple one-pot reaction of indole and \(o\)-phthaldialdehyde. Differently substituted indolyl benzocarbazoles were yielded. Both the indole substitution and the positioning at the molecular scaffold influence the antibacterial activity towards the various strains of \(Enterococcus\) species with the highest relevance to nosocomial infections. Structure-activity relationships are discussed, and the first lead compounds were identified as also being effective in the case of a vancomycin resistance.
KW  - medicine
KW  - antibacterial activity
KW  - synthesis
KW  - derivatives
KW  - structure-activity
KW  - lead structure
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172628
VL  - 22
IS  - 12
ER  - 
TY  - JOUR
A1  - Seethaler, Marius
A1  - Hertlein, Tobias
A1  - Wecklein, Björn
A1  - Ymeraj, Alba
A1  - Ohlsen, Knut
A1  - Lalk, Michael
A1  - Hilgeroth, Andreas
T1  - Novel small-molecule antibacterials against Gram-positive pathogens of Staphylococcus and Enterococcus species
JF  - Antibiotics
N2  - Defeat of the antibiotic resistance of pathogenic bacteria is one great challenge today and for the future. In the last century many classes of effective antibacterials have been developed, so that upcoming resistances could be met with novel drugs of various compound classes. Meanwhile, there is a certain lack of research of the pharmaceutical companies, and thus there are missing developments of novel antibiotics. Gram-positive bacteria are the most important cause of clinical infections. The number of novel antibacterials in clinical trials is strongly restricted. There is an urgent need to find novel antibacterials. We used synthetic chemistry to build completely novel hybrid molecules of substituted indoles and benzothiophene. In a simple one-pot reaction, two novel types of thienocarbazoles were yielded. Both indole substituted compound classes have been evaluated as completely novel antibacterials against the Staphylococcus and Enterococcus species. The evaluated partly promising activities depend on the indole substituent type. First lead compounds have been evaluated within in vivo studies. They confirmed the in vitro results for the new classes of small-molecule antibacterials.
KW  - antibacterial activity
KW  - synthesis
KW  - substituent
KW  - structure-activity
KW  - inhibition
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193130
SN  - 2079-6382
VL  - 8
IS  - 4
ER  -