Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
IUSS-University School for Advanced Studies, 27100 Pavia, Italy.
Molecules. 2020 Mar 9;25(5):1239. doi: 10.3390/molecules25051239.
Tuberculosis is still an urgent global health problem, mainly due to the spread of multi-drug resistant strains, which lead to the need of new more efficient drugs. A strategy to overcome the problem of the resistance insurgence could be the polypharmacology approach, to develop single molecules that act on different targets. Polypharmacology could have features that make it an approach more effective than the classical polypharmacy, in which different drugs with high affinity for one target are taken together. Firstly, for a compound that has multiple targets, the probability of development of resistance should be considerably reduced. Moreover, such compounds should have higher efficacy, and could show synergic effects. Lastly, the use of a single molecule should be conceivably associated with a lower risk of side effects, and problems of drug-drug interaction. Indeed, the multitargeting approach for the development of novel antitubercular drugs have gained great interest in recent years. This review article aims to provide an overview of the most recent and promising multitargeting antitubercular drug candidates.
结核病仍然是一个紧迫的全球健康问题,主要是由于耐多药菌株的传播,这导致需要新的更有效的药物。克服耐药性问题的一种策略可能是多药理学方法,即开发作用于不同靶点的单分子。多药理学可能具有使其比经典的多药治疗更有效的特征,其中高亲和力的不同药物针对同一靶点一起使用。首先,对于具有多个靶点的化合物,发展耐药性的概率应该会大大降低。此外,此类化合物应该具有更高的疗效,并可能显示协同作用。最后,使用单一分子可能与较低的副作用风险和药物相互作用问题相关联。事实上,近年来,开发新型抗结核药物的多靶点方法引起了极大的兴趣。本文综述了最近和最有前途的多靶点抗结核药物候选物。