Wang C C
J Med Chem. 1984 Jan;27(1):1-9. doi: 10.1021/jm00367a001.
I have thus far listed a total of 10 potential targets for antiparasitic chemotherapeutic consideration. This is by no means a completed list. Many more will be added to it with time and with more future findings. Among these 10 targets (summarized in Table I), however, one may gain some insight and see a few interesting general trends: (1) Nucleic acid metabolism and carbohydrate-energy metabolism in protozoan parasites appear to be targets for fruitful chemotherapeutic attacks. Their being useful targets results generally from the deficient metabolism in the protozoan parasites. Thus, the main vulnerability among the protozoan parasites is closely associated with their parasitic nature. (2) Microtubules and nervous systems appear to be the main chemotherapeutic targets in helminths. They differ from those in the host not because of their parasitic nature but, more likely, because of the evolutionary distance separating the mammalian hosts and the primitive metazoa. Thus, free-living nematodes, such as Caenorhabditis elegans, have their microtubules just as susceptible to the benzimidazole anthelmintics as those from the parasitic worms. The motoneuronal map of C. elegans is identical with that of Ascaris lumbricoides. Both worms are similarly immobilized by levamisole, piperazine, avermectins, etc. The dual insecticidal and antiexoparasite activities found in the avermectins and milbemycins may also suggest that the free-living insects and the ticks and lice may have the same GABA nervous system. This main discrepancy between protozoan parasites and metazoan parasites may be partly attributable to the higher mutation rates and higher frequencies of genetic recombination among the protozoa, evidenced by the higher rates of development of drug resistance among them. The fast adaptation to a new environment may be essential for survival, but it would also lead to metabolic deficiencies after the protozoa lived in a luxurious environment for a while. This revelation may suggest that future chemotherapeutic studies on parasitic helminths can utilize free-living helminths as models to eliminate many unnecessary technical difficulties. Also, there perhaps could be a further classification among the parasites to term the protozoa "true parasites" and the helminth "pseudo-parasites" from the viewpoint of chemotherapy.
到目前为止，我总共列出了10个可供抗寄生虫化疗考虑的潜在靶点。这绝不是一个完整的清单。随着时间的推移和未来更多的发现，还会有更多靶点被添加进来。然而，在这10个靶点（总结于表I）中，人们可以获得一些见解并看到一些有趣的总体趋势：（1）原生动物寄生虫中的核酸代谢和碳水化合物 - 能量代谢似乎是富有成效的化疗攻击靶点。它们成为有用靶点通常是由于原生动物寄生虫代谢缺陷。因此，原生动物寄生虫的主要脆弱性与其寄生性质密切相关。（2）微管和神经系统似乎是蠕虫类寄生虫的主要化疗靶点。它们与宿主中的微管和神经系统不同，并非因为其寄生性质，而更可能是由于哺乳动物宿主与原始后生动物之间的进化距离。因此，自由生活的线虫，如秀丽隐杆线虫，其微管与寄生蠕虫的微管一样容易受到苯并咪唑驱虫药的影响。秀丽隐杆线虫的运动神经元图谱与蛔虫的相同。两种蠕虫都同样会被左旋咪唑、哌嗪、阿维菌素等药物麻痹。阿维菌素和米尔倍霉素中发现的双重杀虫和抗外寄生虫活性也可能表明自由生活的昆虫以及蜱和虱子可能具有相同的GABA神经系统。原生动物寄生虫和后生动物寄生虫之间的这种主要差异可能部分归因于原生动物中较高的突变率和较高的基因重组频率，这一点从它们中较高的耐药性发展速率可以得到证明。快速适应新环境对于生存可能至关重要，但这也会导致原生动物在奢侈环境中生活一段时间后出现代谢缺陷。这一发现可能表明，未来对寄生蠕虫的化疗研究可以利用自由生活的蠕虫作为模型来消除许多不必要的技术困难。此外，从化疗的角度来看，也许可以在寄生虫中进一步分类，将原生动物称为“真正的寄生虫”，将蠕虫称为“假寄生虫”。
