University of Tübingen, Institute of Tropical Medicine , Wilhelmstraße 27, D-72074 Tübingen , Germany +49 7071 29 82364 ; +49 7071 295189 ;
Expert Opin Drug Discov. 2013 Nov;8(11):1325-37. doi: 10.1517/17460441.2013.843522. Epub 2013 Oct 3.
The development of new antimalarial drugs remains of the utmost importance, since Plasmodium falciparum has developed resistance against nearly all chemotherapeutics in clinical use. In an effort to contain the resistance of P. falciparum against artemisinins and to further eradication efforts, studies are ongoing to identify novel and more efficacious approaches to develop antimalarials.
The authors review the classical and new approaches to antimalarial drug discovery, with a special emphasis on the various stages of the parasite's life cycle and the different Plasmodium species. The authors discuss the methodologies and strategies for early efficacy testing that aim to narrow down the portfolio of promising compounds.
The increased efforts in the discovery and development of new antimalarial compounds have led to the recognition of new promising hits. However, there is still major roadblock of selecting the most promising compounds and then further testing them in early clinical trials, especially in the current restricted economy. Controlled human malaria infection has much potential for speeding-up the early development process of many drug candidates including those which target the pre-erythrocytic stages.
开发新的抗疟药物仍然至关重要,因为疟原虫已经对几乎所有临床使用的化学疗法产生了耐药性。为了遏制疟原虫对青蒿素的耐药性并进一步开展根除工作,正在进行研究以确定开发抗疟药物的新的、更有效的方法。
作者回顾了抗疟药物发现的经典和新方法,特别强调了寄生虫生命周期的各个阶段和不同的疟原虫物种。作者讨论了旨在缩小有前途的化合物组合范围的早期疗效测试的方法和策略。
在发现和开发新的抗疟化合物方面的努力增加,导致了对新的有前途的候选药物的识别。然而,在当前的经济限制下,仍然存在一个主要障碍,即选择最有前途的化合物,然后在早期临床试验中进一步测试它们,特别是在当前的经济限制下。人体疟疾感染的控制具有很大的潜力,可以加速许多候选药物的早期开发过程,包括针对红细胞前期阶段的药物。