Ferrocene-based inhibitors of hepatitis C virus replication that target NS5A with low picomolar in vitro antiviral activity.

An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1'-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups.

Selenophene-containing inhibitors of type IIA bacterial topoisomerases.

We investigated compounds related to the previously reported antistaphyloccocal agent AVE6971 in an effort to attenuate inhibition of hERG potassium channel current that has been noted for this and related antibacterial drug classes. While most modifications of the original thiophene group compromised antibacterial activity, one selenophene analogue displayed (i) improved activity against the primary target enzyme DNA gyrase, (ii) similar activities against a panel of MRSA clinical isolates, and (iii) reduced hERG channel inhibition.

Exploration of the activity of 7-pyrrolidino-8-methoxyisothiazoloquinolones against methicillin-resistant Staphylococcus aureus (MRSA).

A series of 7-(3'-substituted)pyrrolidino-8-methoxyisothiazoloquinolone (ITQ) analogues were prepared, and their antibacterial potency against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli were compared. Many of these analogues had MIC ≤ 0.25 μg/mL against quinolone-resistant MRSA strains.

New quinolone antibiotics: a survey of the literature from 2005 to 2010.

Importance Of The Field: The quinolone class of antibacterial agents has a proven track record over the past several decades for the treatment of bacterial infections. Their unique mechanism of action and bactericidal properties make them attractive therapeutic agents.

Areas Covered In This Review: Significant research efforts continue to the present day in both academia and industry, which have provided a number of promising drug candidates for further development.

Small molecule inhibitors of E. coli primase, a novel bacterial target.

Bacterial primase is essential for DNA replication in Gram-positive and Gram-negative bacteria. It is also structurally distinct from eukaryotic primases, and therefore an attractive, but under-explored, target for therapeutic intervention. We applied virtual screening to discover primase inhibitors, and subsequently several commercially available analogs of these initial hits showed potent primase inhibition and in vitro antibacterial activity.

Isothiazoloquinolones with enhanced antistaphylococcal activities against multidrug-resistant strains: effects of structural modifications at the 6-, 7-, and 8-positions.

We describe the biological evaluation of isothiazoloquinolones (ITQs) having structural modifications at the 6-, 7-, and 8-positions. Addition of a methoxy substituent to C-8 effected an increase in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and a decrease in cytotoxic activity against Hep2 cells. Removal of fluorine from C-6 or replacement of the C-8 carbon with a nitrogen compromised anti-MRSA activity.

Kinetics of contact electrification between metals and polymers.

Kinetics of charge transfer between metals and polymers was studied using an analytical rolling-sphere tool. The rates of charge transfer were related to the area of contact between contacting surfaces and the tunneling current between them. The derived rate equations accounted for the experimentally observed sigmoidal charging curves.

Isothiazolopyridones: synthesis, structure, and biological activity of a new class of antibacterial agents.

We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequence of seven synthetic transformations. The solid-state structure of 7-chloro-9-ethyl-1-thia-2,4a-diazacyclopenta[b]naphthalene-3,4-dione was determined by X-ray diffraction.

Isothiazoloquinolones containing functionalized aromatic hydrocarbons at the 7-position: synthesis and in vitro activity of a series of potent antibacterial agents with diminished cytotoxicity in human cells.

This report describes 9H-isothiazolo[5,4-b]quinoline-3,4-diones (ITQs) containing aromatic groups at the 7-position that were prepared using palladium-catalyzed cross-coupling and tested against a panel of susceptible and resistant bacteria. In general, these compounds were more effective against Gram-positive than Gram-negative organisms. Many of the ITQs were more potent than contemporary quinolones and displayed a particularly strong antistaphylococcal activity against a clinically important, multi-drug-resistant strain.

Biological evaluation of isothiazoloquinolones containing aromatic heterocycles at the 7-position: In vitro activity of a series of potent antibacterial agents that are effective against methicillin-resistant Staphylococcus aureus.

We synthesized a diverse series of 9H-isothiazolo[5,4-b]quinoline-3,4-diones containing heteroaromatic groups at the 7-position via palladium-catalyzed cross-coupling. Many of these compounds demonstrated potent antistaphylococcal activity (MICs 2 microg/mL) against a multi-drug-resistant strain (ATCC 700699) and low cytotoxic activity (CC(50)>100 microM) against the human cell line Hep2 (laryngeal carcinoma).

A tool for studying contact electrification in systems comprising metals and insulating polymers.

We describe an analytical system for in situ measurement of the charge that develops by contact electrification when a ferromagnetic sphere rolls on the surface of a polymer. This system makes it possible to survey the ability of polymeric surfaces to charge by contact electrification. Because the measurement of charge using this tool does not require physical contact of the charged sphere with the measuring electrode, it also enables the kinetics of charging to be examined.

Electrostatic self-assembly of macroscopic crystals using contact electrification.

Self-assembly of components larger than molecules into ordered arrays is an efficient way of preparing microstructured materials with interesting mechanical and optical properties. Although crystallization of identical particles or particles of different sizes or shapes can be readily achieved, the repertoire of methods to assemble binary lattices of particles of the same sizes but with different properties is very limited. This paper describes electrostatic self-assembly of two types of macroscopic components of identical dimensions using interactions that are generated by contact electrification.

Dynamic self-assembly of rings of charged metallic spheres.

This Letter describes dynamic self-assembly in a system of stainless steel spheres ( approximately 1 mm in diameter) rolling on a flat dielectric surface under the influence of an external magnetic field that rotates parallel to the plane of the surface. As the spheres move, they charge triboelectrically. Self-assembly is mediated by two types of electrostatic interactions among these charges: (i) attraction between negatively charged regions of the surface and positively charged spheres and (ii) repulsion between the like-charged spheres.

A Versatile and High-Yield Route to Active and Well-Defined Catalysts [Ru(bisphosphane)(H)(solvent) ](BF ).

Simple and efficient: Protonation of [Ru(1,2:5,6-η-cod)(η -cot)] (cod=1,5-cyclooctadiene, cot=1,3,5-cyclooctatriene) with HBF ⋅Et O and then reaction with chiral bisphosphane ligands ($_{\rm PP}^{\frown }$=Me-DuPHOS, BINAP, Tol-BINAP, JOSIPHOS) affords the corresponding [Ru($_{\rm PP}^{\frown }$)(H)(η -cot)] or [Ru($_{\rm PP}^{\frown }$)(1,2,3,4,5-η-C H ')] (C H '=2,4-cyclooctadienyl; see scheme). Exposure of these cations to H in solvents (sol) such as acetone, methanol, and THF affords [Ru($_{\rm PP}^{\frown }$)(H)(sol) ] , which are catalysts for (amongst other things) enantioselective hydrogenations of alkenes.