Otarigho Benson, Falade Mofolusho O
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
Department of Biology, Transylvania University, Lexington, KY 40508, USA.
Life (Basel). 2023 Sep 25;13(10):1957. doi: 10.3390/life13101957.
The existing treatment strategy for Schistosomiasis centers on praziquantel, a single drug, but its effectiveness is limited due to resistance and lack of preventive benefits. Thus, there is an urgent need for novel antischistosomal agents. glutathione S-transferase (GST) is an essential parasite enzyme, with a high potential for targeted drug discovery. In this study, we conducted a screening of compounds possessing antihelminth properties, focusing on their interaction with the glutathione S-transferase (GST) protein. We demonstrated the unique nature of GST in comparison to human GST. Evolutionary analysis indicated its close relationship with other parasitic worms, setting it apart from free-living worms such as . Through an assessment of binding pockets and subsequent protein-ligand docking, we identified Scutiaquinone A and Scutiaquinone B, both naturally derived Perylenequinones, as robust binders to GST. These compounds have exhibited effectiveness against similar parasites and offer promising potential as antischistosomal agents.
现有的血吸虫病治疗策略以单一药物吡喹酮为核心，但由于耐药性和缺乏预防效果，其有效性有限。因此，迫切需要新型抗血吸虫药物。谷胱甘肽S-转移酶（GST）是一种重要的寄生虫酶，在靶向药物发现方面具有很高的潜力。在本研究中，我们对具有抗蠕虫特性的化合物进行了筛选，重点关注它们与谷胱甘肽S-转移酶（GST）蛋白的相互作用。我们证明了与人类GST相比，GST具有独特的性质。进化分析表明它与其他寄生蠕虫关系密切，与诸如自由生活蠕虫不同。通过对结合口袋的评估以及随后的蛋白质-配体对接，我们确定了天然来源的苝醌类化合物Scutiaquinone A和Scutiaquinone B是GST的强效结合剂。这些化合物已显示出对类似寄生虫的有效性，并作为抗血吸虫药物具有广阔的潜力。
