Simplificação Molecular como Estratégia para Descoberta e Otimização de Candidatos a Fármacos Antituberculose

Human tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis (Mtb), and has been responsible for the deaths of thousands of people annually.1 Recently, the antimycobacterial activity of 2-(quinolin-4-yloxy)acetamides (Figure 1) and their derivatives has been reported by our research group.2 The compounds have been active against resistant and non-resistant Mtb strains and have exhibited selective inhibition of bacillus growth. Despite the excellent in vitro activity, this class of compounds showed only moderate in vivo activity. This result can be attributed to the metabolic instability of the acetamide group. Therefore, the present work has the objective of synthesizing and characterizing compounds that do not present the acetamide group in a strategy of molecular simplification.