Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, India.
Int J Infect Dis. 2015 Mar;32:50-5. doi: 10.1016/j.ijid.2014.12.031.
Tuberculosis (TB) remains a serious concern more than two decades on from when the World Health Organization declared it a global health emergency. The alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB, has made it exceedingly difficult to control the disease with the existing portfolio of anti-TB chemotherapy. The development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. The development of novel chemical entities requires more than 10 years of research, requiring high-risk investment to become commercially available. Repurposing pre-existing drugs offers a solution to circumvent this mammoth investment in time and funds. In this context, several drugs with known safety and toxicity profiles have been evaluated against the TB pathogen and found to be efficacious against its different physiological states. As the endogenous targets of these drugs in the TB bacillus are most likely to be novel, there is minimal chance of cross-resistance with front-line anti-TB drugs. Also, reports that some of these drugs may potentially have multiple targets means that the possibility of the development of resistance against them is minimal. Thus repurposing existing molecules offers immense promise to tackle extensively drug-resistant TB infections.
结核病（TB）仍然是一个严重的问题，距离世界卫生组织宣布其为全球卫生紧急事件已经过去了二十多年。结核分枝杆菌（导致结核病的病原体）对抗生素的耐药性令人震惊地上升，使得用现有的抗结核化学疗法组合来控制这种疾病变得极其困难。因此，开发具有新型作用机制的有效药物对于解决耐药性问题至关重要。开发新的化学实体需要超过 10 年的研究，需要高风险投资才能上市销售。重新利用现有的药物提供了一种解决方案，可以避免在时间和资金上进行巨额投资。在这种情况下，已经对几种具有已知安全性和毒性特征的药物进行了评估，发现它们对结核病原体的不同生理状态有效。由于这些药物在结核杆菌中的内源性靶标极有可能是新型的，因此与一线抗结核药物发生交叉耐药的可能性很小。此外，有报道称，其中一些药物可能具有多个潜在靶点，这意味着它们产生耐药性的可能性很小。因此，重新利用现有分子为解决广泛耐药性结核病感染提供了巨大的希望。
