Dos Reis Dijovani Batista, Linhares Emily Pacelli Moreira, Dos Santos E Silva Gabriel, do Carmo Ferreira Frederico Henrique, Costa Luiz Antônio Sodré, Ávila Eloah Pereira, de Almeida Mauro Vieira, de Souza Marcus Vinícius Nora, da Silva Lourenço Maria Cristina, Saraiva Mauricio Frota
LaSIMBio-Laboratório de Síntese de Moléculas Bioativas, Institute of Physics and Chemistry, Federal University of Itajubá, Itajubá, Brazil.
NEQC-Núcleo de Estudos em Química Computacional, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
Arch Pharm (Weinheim). 2025 Apr;358(4):e3130. doi: 10.1002/ardp.202400665.
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.
结核病（TB）是一种细菌性疾病，其治疗面临重大挑战。它需要长时间使用高剂量药物，这可能导致各种副作用。这些副作用常常导致患者对治疗的依从性较低，从而增加产生耐药菌株的风险。SQ109是一种从乙胺丁醇衍生而来的第二代药物，已逐渐成为一种有前景的抗结核药物。其骨架的功能化似乎是改善物理化学和生物学性质的一种策略。因此，我们报告了功能化SQ109支架的合成、对结核分枝杆菌H37Rv菌株的体外评估、分子对接模拟以及与靶膜蛋白相互作用的分子动力学。
