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2,3-Diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one heterocycles inhibit growth and block completion of cytokinesis in kinetoplastid parasites
Molecular and Biochemical Parasitology ( IF 1.5 ) Pub Date : 2021-07-21 , DOI: 10.1016/j.molbiopara.2021.111396
Madeline F Malfara 1 , Lee J Silverberg 2 , John DiMaio 3 , Anthony F Lagalante 4 , Mark A Olsen 4 , Ekaterina Madison 3 , Megan L Povelones 1
Affiliation  

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.



中文翻译:

2,3-Diphenyl-2,3-dihydro-4H-1,3-thiaza-4-one 杂环抑制运动质体寄生虫的生长并阻止胞质分裂的完成

动质体寄生虫是具有复杂细胞周期的模型真核生物,在空间和时间上都受到高度调节。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。尽管这些疾病的化学疗法取得了进展,但仍然需要具有强大的抗寄生虫活性且对人类宿主影响最小的化合物库。在研究一系列对这些寄生虫具有潜在活性的 2,3-diphenyl-2,3-dihydro-4 H -1,3-thiaza-4-one 杂环时,我们发现了一种吡啶并噻嗪酮,可抑制单种寄生虫Crithidia fasciculata的生长和布氏锥虫的两个生命周期阶段. 这种抑制在布氏锥虫中更为明显,并且与异常的脱落前细胞周期停滞有关。探索这些和相关化合物在动质体中的作用方式可能会提供工具来探索这些重要生物体中的细胞周期调控。

更新日期:2021-07-27
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