We report the novel chalcone-benzoxaborole hybrids and their structure-activity relationship against Trypanosoma brucei parasites. The 4-NH(2) derivative 29 and 3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH(2)-3-OMe compound 49 showed an IC(50) of 0.010 μg/mL and resulted in 100% survival and zero parasitemia in a murine infection model, which represents one of the most potent compounds discovered to date from the benzoxaborole class that inhibit T. brucei growth.
Realization of highly efficient sulfur electrochemistry, as well as the high capacity of lithium–sulfur (Li–S) batteries, can be achieved by the scientific construction of electrode host materials. In this study, using molten NaCl, a 3D porous nitrogen‐doped carbon with uniformly embedded Co atom clusters (Co/PNC) is developed by pyrolyzing the precursors with NaCl at high temperatures. In the composite structure, a network carbon skeleton containing hierarchical pores acts as an advanced matrix for sulfur electrodes, and the doping of N and Co is subject to inhibit the shuttle of long‐chain lithium polysulfides through chemical adsorption. The Co/PNC, with the optimized amount of Co, delivers an initial specific capacity of 1105.4 mAh g−1 at 0.2 C with a capacity drop of only 0.064% after the cell is charged and discharged for 300 cycles at 1 C, revealing its potential in promoting the large‐scale application of Li–S batteries.
Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R(1) and R(2) groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC50 = 13.7 μM). Aided by ligand-protein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.
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