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首页> 外文期刊>Journal of Molecular Biochemistry >Thianthrene is a novel inhibitor of Leishmania donovani pteridine reductase 1 (PTR1)
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Thianthrene is a novel inhibitor of Leishmania donovani pteridine reductase 1 (PTR1)

机译：噻蒽是利什曼原虫donovani蝶啶还原酶1（PTR1）的新型抑制剂

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摘要

Pteridine reductase 1 (PTR1) from Leishmania donovani is a short chain reductase that catalyses the NADPH-dependent reduction of folates and pterins. It has gained attention as a therapeutic target because it acts as a metabolic bypass for dihydrofolate reductase (DHFR) targeting drugs and is thought to be responsible for the failure of conventional therapies against the trypanosomatids. In the present study, we report the identification of thianthrene as a potent inhibitor of L. donovani PTR1 (LdPTR1) based on both structure-based virtual screening and experimental verification. Thianthrene displayed uncompetitive mixed type inhibition in a recombinant enzyme inhibition assay. In addition, cell based assays and flow cytometry showed that the intracellular amastigotes were inhibited by thianthrene in vitro. The results of our study could be considered for the development of novel therapeutics based on PTR1 inhibition.
机译：来自利什曼原虫的蝶啶还原酶1（PTR1）是一种短链还原酶，可催化NADPH依赖性的叶酸和蝶呤还原。由于它作为靶向二氢叶酸还原酶（DHFR）的代谢旁路，并且被认为是导致针对锥虫的常规疗法失败的原因，它已成为治疗目标。在本研究中，我们报告了基于结构的虚拟筛选和实验验证，鉴定蒽作为多诺氏乳酸杆菌PTR1（LdPTR1）的有效抑制剂。硫蒽在重组酶抑制试验中显示出非竞争性混合型抑制。另外，基于细胞的测定法和流式细胞仪显示，噻蒽可在体外抑制胞内变形虫。我们的研究结果可用于开发基于PTR1抑制的新型疗法。

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