2,3-Diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles inhibit growth and block completion of cytokinesis in kinetoplastid parasites
2,3-Diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles inhibit growth and block completion of cytokinesis in kinetoplastid parasites
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DOI：
10.1016/j.molbiopara.2021.111396
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发表时间：
2021-07-26
影响因子：
1.5
通讯作者：
Povelones, Megan L.
中科院分区：
文献类型：
--
作者：
Malfara, Madeline F.;Silverberg, Lee J.;Povelones, Megan L.
着丝质体寄生虫是具有复杂细胞周期的模式真核生物，具有高度的空间和时间调控。此外，由这些寄生虫引起的疾病继续对全世界的人类和动物健康产生重大影响。虽然这些疾病的化疗已经取得了进展，但仍然需要一种具有强大抗寄生虫活性且对人类宿主影响最小的化合物库。通过对一系列2,3-二苯基-2,3-二氢- 4h -1,3-噻嗪-4- 1杂环化合物的研究，我们发现了一种吡多噻嗪酮，它能抑制单氧寄生虫束状棘虫的生长和布鲁氏锥虫的两个生命周期阶段。这种抑制在布鲁氏体中更为明显，并与不寻常的脱落前细胞周期阻滞有关。探索这些和相关化合物在着丝质体中的作用模式可能为探索这些重要生物体的细胞周期调节提供工具。
Kinetoplastid parasites are model eukaryotes with a complex cell cycle that is highly regulated both spatially and temporally. In addition, diseases caused by these parasites continue to have a significant impact on human and animal health worldwide. While there have been advancements in chemotherapy for these diseases, there is a continual need for an arsenal of compounds that have robust anti-parasite activity with minimal impact on the human host. While investigating a series of 2,3-diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles with potential activity against these parasites, we found a pyridothiazinone that inhibits growth of the monoxenous parasite Crithidia fasciculata and two life cycle stages of Trypanosoma brucei. This inhibition is more pronounced in T. brucei and is associated with an unusual pre-abscission cell cycle arrest. Exploring the mode of action for these and related compounds in kinetoplastids may provide tools with which to explore cell cycle regulation in these important organisms.