The aspartate metabolism pathway

M. Jonathan, B. P. Sulistyo
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Abstract

Recent research has been conducted to find potential new avenues of drug discovery for treating tuberculosis infection. This endless “arms race” is due to the ability of the bacteria to develop resistance towards the already established antibiotic regimen. Various pathways within Mycobacterium tuberculosis are being studied extensively to open new possibilities in drug development. One of which is the aspartate metabolism pathway. This amino acid pathway is proven to be pivotal for the survival of M. tuberculosis both in vitro and in vivo. Furthermore, this pathway also is absent in humans, making it a very promising candidate for further research and development in drug discovery. However, inhibitors against this pathway are not yet available as most suggested inhibitors against the various enzymes within this pathway only made it until the in-silico stage while few studies managed to synthesize their suggested inhibitors and had tested its anti-tuberculosis activity. This review will discuss said attempts in suggesting inhibitors against the critical enzymes that work within this pathway. The inhibitors that are reviewed in this paper are both synthetic and derived from natural products. The multitude of inhibitors proposed and the various enzymes that they are able to inhibit proved that this pathway has potential that is yet to be explored further.
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天冬氨酸代谢途径
最近的研究已经进行,以寻找潜在的新途径的药物发现治疗结核感染。这种无休止的“军备竞赛”是由于细菌对已经建立的抗生素方案产生耐药性的能力。正在广泛研究结核分枝杆菌内的各种途径,以开辟药物开发的新可能性。其中之一是天冬氨酸代谢途径。这种氨基酸途径被证明是结核分枝杆菌在体外和体内存活的关键。此外,这种途径在人类中也不存在,这使得它成为药物发现中进一步研究和开发的非常有前途的候选者。然而,目前还没有针对该途径的抑制剂,因为大多数针对该途径中各种酶的抑制剂仅在硅合成阶段才出现,而很少有研究成功合成了所建议的抑制剂并测试了其抗结核活性。这篇综述将讨论在这一途径中针对关键酶的抑制剂的建议。本文综述的抑制剂既有人工合成的,也有从天然产物中提取的。提出的众多抑制剂和它们能够抑制的各种酶证明了这一途径具有潜力,但有待进一步探索。
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