Development of LpxH Inhibitors Chelating the Active Site Dimanganese Metal Cluster of LpxH.

Despite the widespread emergence of multidrug-resistant nosocomial Gram-negative bacterial infections and the major public health threat it brings, no new class of antibiotics for Gram-negative pathogens has been approved over the past five decades. Therefore, there is an urgent medical need for developing effective novel antibiotics against multidrug-resistant Gram-negative pathogens by targeting previously unexploited pathways in these bacteria. To fulfill this crucial need, we have been investigating a series of sulfonyl piperazine compounds targeting LpxH, a dimanganese-containing UDP-2,3-diacylglucosamine hydrolase in the lipid A biosynthetic pathway, as novel antibiotics against clinically important Gram-negative pathogens.

Evaluation of Manassantin A Tetrahydrofuran Core Region Analogues and Cooperative Therapeutic Effects with EGFR Inhibition.

Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a validated therapeutic target for cancer.