Nzila Alexis
Kenya Medical Research Institute (KEMRI)/Wellcome Trust Collaborative Research Program, PO Box 230, 80108, Kilifi, Kenya.
J Antimicrob Chemother. 2006 Jun;57(6):1043-54. doi: 10.1093/jac/dkl104. Epub 2006 Apr 14.
Chemotherapy remains the most important means of controlling malaria, one of the deadliest infectious parasitic diseases in the world. Antimalarial antifolates have been central for prophylaxis and treatment of malaria. This drug family was discovered in the 1940s, during the Second World War, and molecules that are currently in clinical use were discovered at that time. Since the 1940s, no new antimalarial antifolates have been developed that have reached Phase I/II stages. Limited work has been carried out to exploit the inhibition of the malaria folate pathway as a means of discovering new drugs. In this review, work carried out on antimalarial antifolates since the 1940s up to the present time is discussed in terms of discovery, clinical use, mode of action and mechanism of resistance. New concepts have been presented to improve antimalarial antifolate in vivo efficacy and to identify potent new antifolate agents.
化疗仍然是控制疟疾的最重要手段，疟疾是世界上最致命的传染性寄生虫病之一。抗疟抗叶酸药物一直是疟疾预防和治疗的核心。这个药物家族是在20世纪40年代第二次世界大战期间发现的，目前临床使用的分子也是在那个时候发现的。自20世纪40年代以来，尚未开发出进入I/II期的新型抗疟抗叶酸药物。利用抑制疟疾叶酸途径作为发现新药的手段所开展的工作有限。在这篇综述中，将从发现、临床应用、作用方式和耐药机制等方面讨论自20世纪40年代至今在抗疟抗叶酸药物方面所开展的工作。已提出了新的概念，以提高抗疟抗叶酸药物的体内疗效，并鉴定出有效的新型抗叶酸药物。
