Then R L
Morphochem AG, Microbiology, CH-4058 Basel, Switzerland.
J Chemother. 2004 Feb;16(1):3-12. doi: 10.1179/joc.2004.16.1.3.
Despite all progress made in the fight against infections caused by bacteria, fungi, protozoa or viruses, there is a need for more and new active agents. Intensive efforts are currently directed against many new and attractive targets, and are hoped to result in new useful agents. The opportunities offered by some known and validated targets are, however, by far not exhausted. Dihydrofolate reductase (DHFR, EC 1.5.1.3) attracted much attention over several decades, which yielded several useful agents. There are excellent chances for new drugs in this field, and they are thought to increase by limiting the spectrum of activity. Whereas trimethoprim seems to present the optimum which can be achieved for a broad spectrum antibacterial agent, specific agents could probably be designed for well defined groups or specific organisms, such as staphylococci among the bacteria, or for a number of parasites, such as Plasmodium falciparum, the fungus Pneumocystis carinii, and several protozoa, such as Trypanosoma, Toxoplasma, and others. This would even extend to herbicides or specific plant pathogens. Achievements and current efforts directed against new DHFR-inhibitors are reviewed, considering only the most recent literature.
尽管在对抗由细菌、真菌、原生动物或病毒引起的感染方面已取得了所有进展，但仍需要更多新型活性剂。目前，大量的努力都集中在许多新的、有吸引力的靶点上，有望产生新的有用药物。然而，一些已知且经过验证的靶点所提供的机会远未穷尽。几十年来，二氢叶酸还原酶（DHFR，EC 1.5.1.3）备受关注，由此产生了几种有用的药物。该领域有很好的新药研发机会，并且人们认为通过限制活性谱可以增加此类机会。虽然甲氧苄啶似乎代表了广谱抗菌剂所能达到的最佳效果，但可能可以针对特定的群体或特定的生物体设计特异性药物，例如细菌中的葡萄球菌，或者针对多种寄生虫，如恶性疟原虫、真菌卡氏肺孢子虫，以及几种原生动物，如锥虫、弓形虫等。这甚至可能扩展到除草剂或特定的植物病原体。本文仅参考最新文献，综述了针对新型二氢叶酸还原酶抑制剂的研究成果和当前进展。
