University of Cape Town, Department of Chemistry, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa.
Future Med Chem. 2011 Sep;3(11):1413-26. doi: 10.4155/fmc.11.95.
The emergence and spread of drug resistance in the malaria parasite Plasmodium falciparum as well as multi- and extremely drug-resistant forms of Mycobacterium tuberculosis, the causative agent of TB, could hamper the control of these diseases. For instance, there are indications that the malaria parasite is becoming resistant to artemisinin derivatives, drugs that form the backbone of antimalarial combination therapy. Likewise, Mycobacterium tuberculosis strains that are multidrug-resistant or extremely drug-resistant to first- and second-line drugs have been associated with increased mortality. Thus, more than ever, new antimalarials and anti-TB drugs are needed. One of the strategies to discover new drugs is to reposition or repurpose existing drugs, thus reducing the cost and time of drug development. In this review, we discuss how this concept has been used in the past to discover antimalarial and anti-TB drugs, and summarize strategies that can lead to the discovery and development of new drugs.
疟原虫(Plasmodium falciparum)对青蒿素衍生物的耐药性以及结核分枝杆菌(Mycobacterium tuberculosis)多重耐药和极端耐药形式的出现和传播可能会阻碍这些疾病的控制。例如,有迹象表明,疟原虫对青蒿素衍生物产生了耐药性,而青蒿素衍生物是抗疟联合疗法的核心药物。同样,对一线和二线药物具有多重耐药或极端耐药的结核分枝杆菌菌株与死亡率的增加有关。因此,比以往任何时候都更需要新的抗疟药和抗结核药物。发现新药的策略之一是重新定位或重新利用现有药物,从而降低药物开发的成本和时间。在这篇综述中,我们讨论了过去如何利用这一概念来发现抗疟药和抗结核药物,并总结了可能导致发现和开发新药的策略。