publications of the research group compound profiling and screening
(COPS)http://hdl.handle.net/10033/6205382024-03-29T09:03:07Z2024-03-29T09:03:07ZBuchwald-Hartwig versus Microwave-Assisted Amination of Chloroquinolines: En Route to the Pyoverdin ChromophoreSeubert, PhilippFreund, MarcelRudolf, RichardLin, YulinAltevogt, LucaBilitewski, UrsulaBaro, AngelikaLaschat, Sabinehttp://hdl.handle.net/10033/6226032020-11-24T01:42:17Z2020-07-22T00:00:00ZBuchwald-Hartwig versus Microwave-Assisted Amination of Chloroquinolines: En Route to the Pyoverdin Chromophore
Seubert, Philipp; Freund, Marcel; Rudolf, Richard; Lin, Yulin; Altevogt, Luca; Bilitewski, Ursula; Baro, Angelika; Laschat, Sabine
The reaction of 2-chloro-3-nitroquinoline and a series of amines and aminoalkanoates under
basic microwave-mediated conditions and Buchwald-Hartwig amination conditions is
reported. The microwave irradiation favored the reaction with amines, resulting in yields up to
80%, while amino acid functionalization gave yields comparable to those of BuchwaldHartwig amination. (2R)-4-[(6,7-dimethoxy-3-nitroquinolinyl)amino]-2-hydroxybutanoate
could be successfully cyclized to the pyoverdin chromophore, a subunit of siderophores.
2020-07-22T00:00:00ZSynthesis and Biological Evaluation of a Library of AGE-Related Amino Acid Triazole CrosslinkersIcik, EsraJolly, AnthonyLöffler, PaulAgelidis, NektariosBugdayci, BakiyeAltevogt, LucaBilitewski, UrsulaBaro, AngelikaLASCHAT, SABINEhttp://hdl.handle.net/10033/6224912020-10-01T03:02:55Z2020-08-10T00:00:00ZSynthesis and Biological Evaluation of a Library of AGE-Related Amino Acid Triazole Crosslinkers
Icik, Esra; Jolly, Anthony; Löffler, Paul; Agelidis, Nektarios; Bugdayci, Bakiye; Altevogt, Luca; Bilitewski, Ursula; Baro, Angelika; LASCHAT, SABINE
Three N‐Boc‐protected amino acids, l‐serine, l‐aspartic, and l‐glutamic acid, were either converted into their methyl azidoalkanoates or various alkynes via Bestmann‐Ohira strategy or via reaction with propargylamine and propargyl bromide, respectively. The Cu‐catalyzed click reaction provided a library of amino acid based triazoles, which were further N‐methylated to triazolium iodides or deprotected and precipitated as free amino acid triazole dihydrochlorides. The biological properties of all derivatives were investigated by cytotoxicity assay (against L929 mouse fibroblasts) and broth microdilution method (E. coli ΔTolC and S. aureus). First results reveal complete inactivity for triazolium iodides with cell viabilities and microbial growths nearly 100 %, indicating them as possible analogs of advanced glycation endproducts (AGEs).
2020-08-10T00:00:00ZPolyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds.Zapol'skii, Viktor ABilitewski, UrsulaKupiec, Sören RRamming, IsabellKaufmann, Dieter Ehttp://hdl.handle.net/10033/6223772020-08-04T02:35:32Z2020-06-21T00:00:00ZPolyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds.
Zapol'skii, Viktor A; Bilitewski, Ursula; Kupiec, Sören R; Ramming, Isabell; Kaufmann, Dieter E
Substituted nitrogen heterocycles are structural key units in many important pharmaceuticals. A new synthetic approach towards heterocyclic compounds displaying antibacterial activity against Staphylococcus aureus or cytotoxic activity has been developed. The selective synthesis of a series of 64 new N-heterocycles from the three nitrobutadienes 2-nitroperchloro-1,3-butadiene, 4-bromotetrachloro-2-nitro-1,3-butadiene and (Z)-1,1,4-trichloro-2,4-dinitrobuta-1,3-diene proved feasible. Their reactions with N-, O- and S-nucleophiles provide rapid access to push-pull substituted benzoxazolines, benzimidazolines, imidazolidines, thiazolidinones, pyrazoles, pyrimidines, pyridopyrimidines, benzoquinolines, isothiazoles, dihydroisoxazoles, and thiophenes with unique substitution patterns. Antibacterial activities of 64 synthesized compounds were examined. Additionally, seven compounds (thiazolidinone, nitropyrimidine, indole, pyridopyrimidine, and thiophene derivatives) exhibited a significant cytotoxicity with IC50-values from 1.05 to 20.1 µM. In conclusion, it was demonstrated that polyhalonitrobutadienes have an interesting potential as structural backbones for a variety of highly functionalized, pharmaceutically active heterocycles.
2020-06-21T00:00:00ZInhibition of Respiration of Candida albicans by Small Molecules Increases Phagocytosis Efficacy by Macrophages.Cui, ShunaLi, MinghuiHassan, Rabeay Y AHeintz-Buschart, AnnaWang, JunsongBilitewski, Ursulahttp://hdl.handle.net/10033/6222602020-05-14T01:36:30Z2020-04-15T00:00:00ZInhibition of Respiration of Candida albicans by Small Molecules Increases Phagocytosis Efficacy by Macrophages.
Cui, Shuna; Li, Minghui; Hassan, Rabeay Y A; Heintz-Buschart, Anna; Wang, Junsong; Bilitewski, Ursula
Candida albicans adapts to various conditions in different body niches by regulating gene expression, protein synthesis, and metabolic pathways. These adaptive reactions not only allow survival but also influence the interaction with host cells, which is governed by the composition and structure of the fungal cell wall. Numerous studies had shown linkages between mitochondrial functionality, cell wall integrity and structure, and pathogenicity. Thus, we decided to inhibit single complexes of the respiratory chain of C. albicans and to analyze the resultant interaction with macrophages via their phagocytic activity. Remarkably, inhibition of the fungal bc1 complex by antimycin A increased phagocytosis, which correlated with an increased accessibility of β-glucans. To contribute to mechanistic insights, we performed metabolic studies, which highlighted significant changes in the abundance of constituents of the plasma membrane. Collectively, our results reinforce the strong linkage between fungal energy metabolism and other components of fungal physiology, which also determine the vulnerability to immune defense reactions.IMPORTANCE The yeast Candida albicans is one of the major fungal human pathogens, for which new therapeutic approaches are required. We aimed at enhancements of the phagocytosis efficacy of macrophages by targeting the cell wall structure of C. albicans, as the coverage of the β-glucan layer by mannans is one of the immune escape mechanisms of the fungus. We unambiguously show that inhibition of the fungal bc1 complex correlates with increased accessibilities of β-glucans and improved phagocytosis efficiency. Metabolic studies proved not only the known direct effects on reactive oxygen species (ROS) production and fermentative pathways but also the clear downregulation of the ergosterol pathway and upregulation of unsaturated fatty acids. The changed composition of the plasma membrane could also influence the interaction with the overlying cell wall. Thus, our work highlights the far-reaching relevance of energy metabolism, indirectly also for host-pathogen interactions, without affecting viability.
2020-04-15T00:00:00Z