Semisynthetic artemisinins and other bioactive peroxides are best known for their powerful antimalarial activities, and they also show substantial activity against schistosomes-another hemoglobin-degrading pathogen. Building on this discovery, we now describe the initial structure-activity relationship (SAR) of antischistosomal ozonide carboxylic acids OZ418 (2) and OZ165 (3). Irrespective of lipophilicity, these ozonide weak acids have relatively low aqueous solubilities and high protein binding values. Ozonides with para-substituted carboxymethoxy and N-benzylglycine substituents had high antischistosomal efficacies. It was possible to increase solubility, decrease protein binding, and maintain the high antischistosomal activity in mice infected with juvenile and adult Schistosoma mansoni by incorporating a weak base functional group in these compounds. In some cases, adding polar functional groups and heteroatoms to the spiroadamantane substructure increased the solubility and metabolic stability, but in all cases decreased the antischistosomal activity.

中文翻译：

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抗血吸虫病的臭氧性羧酸的构效关系。

半合成青蒿素和其他具有生物活性的过氧化物以其强大的抗疟疾活性而闻名，它们还对血吸虫（另一种降解血红蛋白的病原体）显示出显着的活性。基于此发现，我们现在描述抗血吸虫臭氧化物分子OZ418（2）和OZ16​​5（3）的初始构效关系（SAR）。与亲脂性无关，这些臭氧化物弱酸具有相对较低的水溶性和较高的蛋白质结合值。具有对位取代的羧基甲氧基和N-苄基甘氨酸取代基的臭氧具有高的抗血吸虫病功效。有可能增加溶解度，减少蛋白质结合，并通过在这些化合物中掺入弱碱性官能团，在感染了未成年和成年曼氏血吸虫的小鼠中维持较高的抗血吸虫病活性。在某些情况下，向螺金刚烷亚结构中添加极性官能团和杂原子可增加溶解度和代谢稳定性，但在所有情况下均会降低抗血吸虫活性。