Tuberculosis (TB) is one of the main causes of death from a single pathological agent, Mycobacterium tuberculosis (Mtb). In addition, the emergence of drug-resistant TB strains has exacerbated even further the treatment outcome of TB patients. It is thus needed the search for new therapeutic strategies to improve the current treatment and to circumvent the resistance mechanisms of Mtb. The shikimate kinase (SK) is the fifth enzyme of the shikimate pathway, which is essential for the survival of Mtb. The shikimate pathway is absent in humans, thereby indicating SK as an attractive target for the development of anti-TB drugs. In this work, a combination of in silico and in vitro techniques was used to identify potential inhibitors for SK from Mtb (MtSK). All compounds of our in-house database (Centro de Pesquisas em Biologia Molecular e Funcional, CPBMF) were submitted to in silico toxicity analysis to evaluate the risk of hepatotoxicity. Docking experiments were performed to identify the potential inhibitors of MtSK according to the predicted binding energy. In vitro inhibitory activity of MtSK-catalyzed chemical reaction at a single compound concentration was assessed. Minimum inhibitory concentration values for in vitro growth of pan-sensitive Mtb H37Rv strain were also determined. The mixed approach implemented in this work was able to identify five compounds that inhibit both MtSK and the in vitro growth of Mtb.

结核病 (TB) 是单一病原体结核分枝杆菌( Mtb )导致死亡的主要原因之一。此外，耐药结核菌株的出现进一步恶化了结核病患者的治疗结果。因此需要寻找新的治疗策略来改善目前的治疗并规避Mtb的耐药机制。莽草酸激酶 (SK) 是莽草酸途径的第五种酶，对Mtb的存活至关重要. 人类中不存在莽草酸途径，因此表明 SK 是开发抗结核药物的有吸引力的靶标。在这项工作中，结合使用计算机和体外技术从Mtb ( Mt SK) 中鉴定 SK 的潜在抑制剂。我们内部数据库（Centro de Pesquisas em Biologia Molecular e Funcional，CPBMF）中的所有化合物都提交给计算机毒性分析以评估肝毒性风险。进行对接实验以根据预测的结合能鉴定Mt SK 的潜在抑制剂。Mt的体外抑制活性评估了单一化合物浓度下 SK 催化的化学反应。还确定了泛敏感Mtb H37Rv 菌株体外生长的最低抑制浓度值。在这项工作中实施的混合方法能够识别出五种抑制Mt SK 和Mtb体外生长的化合物。