Synthesis and biological evaluation of a new class of anti-brucella compounds targeting histidinol dehydrogenase: α-O-arylketones and α-S-arylketones derived from histidine

Abstract

Bacterial infections are commonly treated with antibiotic chemotherapy. The biological targets of these antibiotics are at the origin of appearance of resistant bacterial strains. Recently, the development of new approaches, such as the antivirulence strategy leads the medicinal chemist to describe novel targets with a reduced probability of resistance development. Virulence factors, such as enzymes involved in amino acids biosynthesis, have been validated as such targets. In this paper, we describe the synthesis of a new class of histidinol dehydrogenase inhibitors: α-O-arylketones and α-S-aryl ketones derived from histidine.