Modification of Triclosan Scaffold in Search of Improved Inhibitors for Enoyl‐Acyl Carrier Protein (ACP) Reductase in Toxoplasma gondii

Through our focused effort to discover new and effective agents against toxoplasmosis, a structure‐based drug design approach was used to develop a series of potent inhibitors of the enoyl‐acyl carrier protein (ACP) reductase (ENR) enzyme in Toxoplasma gondii (TgENR). Modifications to positions 5 and 4′ of the well‐known ENR inhibitor triclosan afforded a series of 29 new analogues. Among the resulting compounds, many showed high potency and improved physicochemical properties in comparison with the lead. The most potent compounds 16 a and 16 c have IC₅₀ values of 250 nM against Toxoplasma gondii tachyzoites without apparent toxicity to the host cells. Their IC₅₀ values against recombinant TgENR were found to be 43 and 26 nM , respectively. Additionally, 11 other analogues in this series had IC₅₀ values ranging from 17 to 130 nM in the enzyme‐based assay. With respect to their excellent in vitro activity as well as improved drug‐like properties, the lead compounds 16 a and 16 c are deemed to be excellent starting points for the development of new medicines to effectively treat Toxoplasma gondii infections.     

Operating conditions of the slotted hollow cathode UV Cu+laser

The performance of the UV Cu+ laser in a slotted hollow cathode has been investigated experimentally. The laser power dependent on discharge current, neon pressure, cathode length, and laser mirror transmission has been measured. The optimum neon pressure was found to be 13 mbar. Single-pass gains about 8 percent . m^-1have been evaluated. The observed changes in the slot shape by sputtering during 100 h of operation are briefly discussed. The experimental results are compared to a recent sputtering theory and reasonable agreement is found. The sputtering theory, the spontaneous intensity measurements, and the evaluated gains are used to calculate the number densities of the5sCu+ levels. Laser power is calculated from single-pass gains and agreement with experimental results is obtained.