Synthesis and evaluation of inhibitors of Mycobacterium tuberculosis UGM using bioisosteric replacement.

There is a dearth of tuberculosis (TB) drug development activity as current therapeutic treatments are inadequate due to the appearance of drug-resistant TB. The enzyme UDP-galactopyranose mutase (UGM) is involved in the biosynthesis of galactan which is essential for cell wall integrity and bacterial viability. Its inhibition has thus been featured as profitable strategy for anti-TB drug discovery. In this study, we report on the synthesis of amides derived from rosmarinic acid, their inhibitory effect towards purified UGM using three distinct biochemical assays: FP, HPLC and SPR. The rosmarinic amides generally showed a significantly higher affinity for UGM than the corresponding rosmarinic ester. In particular, compound 5h displayed interesting binding affinity values (Kd = 58 ± 7, 63 ± 9 µM towards KpUGM and MtUGM respectively). Furthermore, a new UGM SPR assay was established and confirmed that 5h binds to UGM with a dissociation constant of 104.8 ± 6.5 µM. Collectively, this study validates the amide bioisosteric strategy which has been successfully implemented to develop UGM inhibitors from rosmarinic acid, providing a substantial basis for further design of novel UGM inhibitors and anti-mycobacterial agents.

Advanced Se3 P4 @C Anode with Exceptional Cycling Life for High Performance Potassium-Ion Batteries.

Potassium-ion batteries have attracted increasing attention for next-generation energy storage systems due to their high energy density and abundance of potassium. However, the lack of suitable anode highly hampers its practical application due to the large ionic radius of K+ . Herein, a Se3 P4 @mesoporous carbon (Se3 P4 @C) composite is reported as a high-performance anode for potassium-ion batteries. The Se3 P4 @C composite is synthesized through an in situ combination reaction between red phosphorus and Se within a porous carbon matrix. In this way, the nano-sized Se3 P4 is well confined in the porous carbon and thus exhibits a close contact with the carbon matrix. This can significantly improve the conductivity and alleviate the volume change during the cycling process. As a result, the Se3 P4 @C exhibits a high reversible initial capacity of 1036.8 mAh g-1 at a current density of 50 mA g-1 as well as an excellent cycle performance with a capacity decay of 0.07% per cycle over 300 cycles under 1000 mA g-1 . In terms of high specific capacity and stable cycling performance, the Se3 P4 @C anode is a promising candidate for advanced potassium-ion batteries.