1-(1H-indol-3-yl)ethanamine derivatives as potent Staphylococcus aureus NorA efflux pump inhibitors.

The synthesis of 37 1-(1H-indol-3-yl)ethanamine derivatives, including 12 new compounds, was achieved through a series of simple and efficient chemical modifications. These indole derivatives displayed modest or no intrinsic anti-staphylococcal activity. By contrast, several of the compounds restored, in a concentration-dependent manner, the antibacterial activity of ciprofloxacin against Staphylococcus aureus strains that were resistant to fluoroquinolones due to overexpression of the NorA efflux pump.

Combinatorial discovery of fluorescent pharmacophores by multicomponent reactions in droplet arrays.

Fluorescence imaging in clinical diagnostics and biomedical research relies to a great extent on the use of small organic fluorescent probes. Because of the difficulty of combining fluorescent and molecular-recognition properties, the development of such probes has been severely restricted to a number of well-known fluorescent scaffolds. Here we demonstrate that autofluorescing druglike molecules are a valuable source of bioimaging probes.

Synthesis and evaluation of 1-(1H-indol-3-yl)ethanamine derivatives as new antibacterial agents.

A collection of 3-substituted indole derivatives was prepared using nucleophilic addition of indoles to nitrones. The compounds were then tested for their antibacterial activity against almost thirty bacterial strains representative of common human pathogens. Two types of indolic molecules inhibit the growth of Staphylococcus aureus, including MRSA and VISA strains, with MIC values ranging from 8 to 16 mg/L.

A direct and versatile access to alpha,alpha-disubstituted 2-pyrrolidinylmethanols by SmI2-mediated reductive coupling.

Various alpha,alpha-disubstituted 2-pyrrolidinylmethanols are efficiently prepared in a single step from ketones using a SmI2-mediated cross-coupling with 1-pyrroline N-oxide. The N-hydroxy-alpha,alpha-diphenylprolinol is also easily prepared and resolved.

Fluorogenic ester substrates to assess proteolytic activity.

The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluorescein in three steps with common commercially available precursors, they all generate bright green fluorescence upon proteolysis. Their particular structure allows the same substrate be used to report enzymatic activity of various proteases from serine and cysteine superfamilies.

Fluorescein-based amino acids for solid phase synthesis of fluorogenic protease substrates.

An efficient synthesis of new type fluorescent amino acids is described. The Fmoc-protected dyes can be prepared in a four-step procedure with approximately 30% overall yield from aminofluoresceins and other inexpensive commercially available precursors. The dyes are much more photostable compared to fluorescein and exhibit constant pH-independent fluorescence that is advantageous in biological applications.