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Methicillin-resistant Staphylococcus aureus (MRSA) causes severe infections with only few effective antibiotic therapies currently available. To approach this challenge, chemical entities with a novel and resistance-free mode of action are desperately needed. Here, we introduce a new hydroxyamide compound that effectively reduces the expression of devastating toxins in various S. aureus and MRSA strains. The molecular mechanism was investigated by transcriptome analysis as well as by affinity-based protein profiling. Down-regulation of several pathogenesis associated genes suggested the inhibition of a central virulence-related pathway. Mass spectrometry-based chemical proteomics revealed putative molecular targets. Systemic treatment with the hydroxyamide showed significant reduction of abscess sizes in a MRSA mouse skin infection model. The absence of resistance development in vitro further underlines the finding that targeting virulence could lead to prolonged therapeutic options in comparison to antibiotics that directly address bacterial survival. Disarming MRSA: A new hydroxyamide compound effectively reduces the expression of devastating toxins in various S. aureus and MRSA strains. The molecular mechanism was investigated by transcriptome analysis, as well as by affinity-based protein profiling. Systemic treatment with the hydroxyamide showed significant reduction of abscess sizes in an MRSA mouse skin infection model.

A synthetic route to the C-nucleoside that bears benzophenone as a DNA base substitution directly at the anomeric center of the 2′- deoxyribofuranoside was worked out. Furthermore, the -anomer of this artificial nucleoside was converted synthetically into the corresponding DNA building block and incorporated into two representative oligonucleotides by automated phosphoramidite chemistry. The chromophore-modified DNA was characterized by methods of optical spectroscopy. The absorption band at ～350 nm can be used for selective excitation of the benzophenone chromophore outside the nucleic acid absorption range, which makes the benzophenone nucleoside potentially useful for photochemical and photobiological applications. Georg Thieme Verlag Stuttgart · New York.

The first asymmetric synthesis of novel, potent photoreactive γ-secretase inhibitors 2 and 3 has been accomplished. Two Stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing γ-secretase activity in the plasma membrane of intact cells.

2-Aryl substituted benzimidazoles and imidazo[4,5]pyridines are disclosed as inhibitors of Cds1 and useful as adjuvants to chemotherapy or radiation therapy in the treatment of cancer.

A transition state analogue inhibitor, boronic acid benzophenone (BBP) photoprobe, was used to study the differences in the topology of the S1 pocket of chemically modified mutant enzymes (CMMs). The BBP proved to be an effective competitive in

The photochemical reactions of (p-benzoylphenyl)diphenylmethyl (1) and (p-benzoylphenyl)bis(4-tert-butylphenyl)methyl (2) in various solvents were investigated. The photophysical parameters of the first excited doublet state of the radicals were measured using spectroscopic and kinetic methods and led to a 'molecular rotor' model to characterize the excited-state behavior. The charge-transfer excited state for both radicals was observed. Photoproducts separated from the photolysis of 1 and 2 in benzene suggest photodecomposition proceeds via H-abstraction (55%), fragmentation (20%), cyclization (10%), and addition (10%).

Diphenyldiazomethanes possessing stable tert-butylaminoxyl and Ullman's 'nitronyl nitroxide' radicals were prepared. The corresponding diphenylcarbenes substituted with the free radicals were generated by photolysis of the parent diazomethanes. From EPR f

The ground state of the hydroxydiphenylmethyl radical (1) leads to benzpinacol (2) through head-to-head coupling and the diols 3 as cross-coupling product. In contrast, under the high-intensity conditions of the laser-jet photolysis, the excited radical 1* couples in the para position to afford the benzophenone derivatives 4 (head-to-tail coupling) (higher spin density at the para position/AM1 calculations). The major two-photon product is benzhydrol (5). The pronounced increase in hydrogen atom abstraction from MeOH to iPrOH by 1* is explained in terms of the greater electrophilic character of the electronically excited radical 1* versus its ground state.

A series of compounds, each containing a triplet energy donor and an acceptor separated by a rigid spacer, has been designed and synthesized.The 1,4-cyclohexanediyl moiety is employed as the spacer for the series.The rates of intramolecular triplet energy

Emission spectra of intra- and intermolecular exciplex systems of benzophenone and N,N-dimethylaniline were studied in detail at low temperature.Two new emissions were observed for the first time in the present work in addition to the well-known phosphore

1-(p-alkanoylphenyl) alkanols, e.g., 1-(p-acetophenyl)-2,2-dimethylpropanol, are prepared from p-alkanoylphenyl Grignard reagents and alkyl and aryl aldehydes or acyl or aroyl halides and are useful as hypolipidemic and anti-diabetic agents.