Synthesis, Antituberculosis Evaluation and Structure–Activity Relationships of New SQ109 Analogs

Tuberculosis (TB) is a bacterial disease that poses significant challenges in its treatment. It requires prolonged use of high doses of medication, which can lead to various side effects. These side effects often contribute to low patient adherence to treatment, thereby increasing the risk of developing drug-resistant strains. The SQ109 is a second-generation agent developed from ethambutol that has been emerging as a promising TB agent. The functionalization of its skeleton appears as a strategy to improve the physicochemical and biological properties. Hence, we report the synthesis of functionalized SQ109 scaffolds, the in vitro evaluation against Mycobacterium tuberculosis H37Rv strains, molecular docking simulations, and molecular dynamics of the interactions with the target membrane protein.