A major constraint in reducing tuberculosis epidemic is the emergence of strains resistant to one or more of clinically approved antibiotics, which emphasizes the need of novel drugs with novel targets. Genetic knockout strains of Mycobacterium tuberculosis (Mtb) have established that tryptophan (Trp) biosynthesis is essential for the bacterium to survive in vivo and cause disease in animal models. An anthranilate-like compound, 6-FABA, was previously shown to synergize with the host immune response to Mtb infection in vivo. Herein, we present a class of anthranilate-like compounds endowed with good antimycobacterial activity and low cytotoxicity. We show how replacing the carboxylic moiety with a hydrazide led to a significant improvement in both activity and cytotoxicity relative to the parent compound 6-FABA. Several new benzohydrazides (compounds 20–31, 33, 34, 36, 38 and 39) showed good activities against Mtb (0.625 ≤ MIC≤6.25 μM) and demonstrated no detectable cytotoxicity against Vero cell assay (CC₅₀ ≥ 1360 μM). The target preliminary studies confirmed the hypothesis that this new class of compounds inhibits Trp biosynthesis. Taken together, these findings indicate that fluorophenylbenzohydrazides represent good candidates to be assessed for drug discovery.

减少结核病流行的一个主要制约因素是对一种或多种临床批准的抗生素产生耐药性的菌株的出现，这强调了对具有新靶点的新药物的需求。结核分枝杆菌( Mtb ) 的基因敲除菌株已证实色氨酸 (Trp) 生物合成对于细菌在体内存活并在动物模型中引起疾病​​至关重要。一种邻氨基苯甲酸类化合物6-FABA先前已被证明可以与宿主体内对Mtb感染的免疫反应产生协同作用。在此，我们提出了一类具有良好抗分枝杆菌活性和低细胞毒性的邻氨基苯甲酸盐类化合物。我们展示了用酰肼取代羧基部分如何导致相对于母体化合物6-FABA的活性和细胞毒性显着改善。几种新的苯甲酰肼（化合物20 – 31 、 33 、 34 、 36 、 38和39 ）对Mtb表现出良好的活性（0.625 ≤ MIC ≤ 6.25 μM），并且对 Vero 细胞测定（CC ₅₀ ≥ 1360 μM）没有可检测到的细胞毒性。目标初步研究证实了此类新型化合物抑制色氨酸生物合成的假设。总而言之，这些发现表明氟苯基苯甲酰肼是药物发现评估的良好候选者。