Schlitzer Martin
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35032 Marburg, Germany.
ChemMedChem. 2007 Jul;2(7):944-86. doi: 10.1002/cmdc.200600240.
Since ancient times, humankind has had to struggle against the persistent onslaught of pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease worldwide. Considerable success in gaining control over malaria was achieved in the 1950s and 60s through landscaping measures, vector control with the insecticide DDT, and the widespread administration of chloroquine, the most important antimalarial agent ever. In the late 1960s, the final victory over malaria was believed to be within reach. However, the parasites could not be eradicated because they developed resistance against the most widely used and affordable drugs of that time. Today, cases of malaria infections are on the rise and have reached record numbers. This review gives a short description of the malaria disease, briefly addresses the history of antimalarial drug development, and focuses on drugs currently available for malaria therapy. The present knowledge regarding their mode of action and the mechanisms of resistance are explained, as are the attempts made by numerous research groups to overcome the resistance problem within classes of existing drugs and in some novel classes. Finally, this review covers all classes of antimalarials for which at least one drug candidate is in clinical development. Antimalarial agents that are solely in early development stages will be addressed in a separate review.
自古以来，人类就不得不与致病性微生物的持续侵袭作斗争。如今，疟疾仍是全球最重要的传染病。20世纪50年代和60年代，通过环境美化措施、使用杀虫剂滴滴涕进行病媒控制以及广泛施用当时最重要的抗疟药物氯喹，在控制疟疾方面取得了相当大的成功。20世纪60年代末，人们认为对疟疾的最终胜利即将实现。然而，由于寄生虫对当时使用最广泛且价格低廉的药物产生了耐药性，所以无法将其根除。如今，疟疾感染病例正在增加，并已达到创纪录的数量。本综述简要介绍了疟疾疾病，简要阐述了抗疟药物研发的历史，并重点介绍了目前可用于疟疾治疗的药物。文中解释了关于其作用方式和耐药机制的现有知识，以及众多研究团队为克服现有药物类别和一些新型药物类别中的耐药问题所做的努力。最后，本综述涵盖了所有至少有一种候选药物处于临床开发阶段的抗疟药物类别。仅处于早期开发阶段的抗疟药物将在另一篇综述中讨论。
