| 摘要 |
The invention provides methods for determining and evaluating the in vitro-in vivo activity relationship of the efficacy of families of compounds for infectious diseases such as tuberculosis. The validity of the methods can be confirmed by evaluation of the compounds in animal models, for example, in murine models of tuberculosis. Examples of families of antibacterial compounds that can be evaluated for in vivo efficacy using the in vitro methods described herein include benzimidazoles, pyridopyrazines, pteridines, diphenyl ethers, beta-lactams, PBP inhibitors, and compounds that are non-ribonucleic acid and protein synthesis inhibitors. The methods can be used to evaluate classes of small molecule compounds and inhibitors that may be effective against any bacterial pathogen. The methods aid the identification of compounds, such as various benzimidazoles, with modes of action having activity against clinical isolates, as well as non-replicating persistent bacilli, which can therefore enhance current clinical therapeutic regimens. |
