Cell-Based Fluorescent Screen Amenable to HTS to Identify Inhibitors of Bacterial Translation Initiation.

A strategy that can be applied to the research of new molecules with antibacterial activity is to look for inhibitors of essential bacterial processes within large collections of chemically heterogeneous compounds. The implementation of this approach requires the development of assays aimed at the identification of molecules interfering with specific cell pathways that can also be used in high-throughput analysis of large chemical libraries. Here, we describe a fluorescence-based whole-cell assay in Escherichia coli devised to find inhibitors of the translation initiation pathway.

N═N Bond Cleavage by Tantalum Hydride Complexes: Mechanistic Insights and Reactivity.

The reaction of [TaCpX] (Cp = η-CMe, η-CHSiMe, η-CHMe; X = Cl, Br) with SiHPh resulted in the formation of the dinuclear hydride tantalum(IV) compounds [(TaCpX)(μ-H)], structurally identified by single-crystal X-ray analyses. These species react with azobenzene to give the mononuclear imide complex [TaCpX(NPh)] along with the release of molecular hydrogen. Analogous reactions between the [{Ta(η-CMe)X}(μ-H)] derivatives and the cyclic diazo reagent benzo[]cinnoline afford the biphenyl-bridged (phenylimido)tantalum complexes [{Ta(η-CMe)X}(μ-NCHCHN)] along with the release of molecular hydrogen.

Development of a Novel High-Density [3H]Hypoxanthine Scintillation Proximity Assay To Assess Plasmodium falciparum Growth.

The discovery and development of new antimalarial drugs are becoming imperative because of the spread of resistance to current clinical treatments. The lack of robustly validated antimalarial targets and the difficulties with the building in of whole-cell activity in screening hits are hampering target-based approaches. However, phenotypic screens of structurally diverse molecule libraries are offering new opportunities for the identification of novel antimalarials.

New direct inhibitors of InhA with antimycobacterial activity based on a tetrahydropyran scaffold.

Tetrahydropyran derivative 1 was discovered in a high-throughput screening campaign to find new inhibitors of mycobacterial InhA. Following initial in-vitro profiling, a structure-activity relationship study was initiated and a focused library of analogs was synthesized and evaluated. This yielded compound 42 with improved antimycobacterial activity and low cytotoxicity.