In spite of the medical and technological developments of the last centuries, Tuberculosis (TB) has remained a challenging disease, with a limited number of therapeutic options, particularly in light of the increase in drug-resistant cases. The search for new molecules continues, with several candidates currently in clinical testing and ongoing efforts to identify novel targets. This work summarizes recent developments on anti-TB therapy, starting by discussing the current epidemiologic status and presenting an overview of the history of anti-tuberculosis drug discovery. Special attention is dedicated to five multifunctional enzymes that are regarded as promising targets for new anti-TB drugs: 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase (ATIC); 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBPS)/GTP cyclohydrolase II (GCHII); glutamine dependent NAD+ Synthetase (NadE); chorismate synthase (CS); and Tryptophan synthase (TS). These enzymes are involved in metabolic pathways critical for the M. tuberculosis survival, growth or replication, but that are not expressed in humans or have significant differences in terms of functionality, which makes them appealing targets. Their function, structure, possible catalytic mechanisms, and current inhibition strategies and inhibitors are reviewed and discussed.

尽管过去几个世纪的医学和技术取得了发展，但结核病 (TB) 仍然是一种具有挑战性的疾病，治疗选择有限，特别是鉴于耐药病例的增加。寻找新分子的工作仍在继续，目前有几个候选药物正在进行临床测试，并正在努力寻找新的靶点。这项工作总结了抗结核治疗的最新进展，首先讨论了当前的流行病学状况，并概述了抗结核药物发现的历史。特别关注五种被认为是新型抗结核药物有希望的靶标的多功能酶：5-氨基咪唑-4-甲酰胺核糖核苷酸转化酶/IMP环水解酶（ATIC）；3、4-二羟基-2-丁酮 4-磷酸合酶 (DHBPS)/GTP 环水解酶 II (GCHII)；谷氨酰胺依赖性 NAD+ 合成酶 (NadE)；分支酸合酶 (CS)；和色氨酸合酶 (TS)。这些酶参与了对结核分枝杆菌生存、生长或复制至关重要的代谢途径，但这些酶在人类中没有表达或在功能方面存在显着差异，这使得它们成为吸引人的目标。对其功能、结构、可能的催化机制以及当前的抑制策略和抑制剂进行了回顾和讨论。但在人类身上没有表现出来，或者在功能方面存在显着差异，这使得它们成为吸引人的目标。对其功能、结构、可能的催化机制以及当前的抑制策略和抑制剂进行了回顾和讨论。但在人类身上没有表现出来，或者在功能方面存在显着差异，这使得它们成为吸引人的目标。对其功能、结构、可能的催化机制以及当前的抑制策略和抑制剂进行了回顾和讨论。