Department of Biology, College of Science and Arts, Qassim University, Unaizah 51911, Saudi Arabia; Department of Science Laboratories, College of Science and Arts, Qassim University, King Abdelaziz Road, Ar Rass 51921, Saudi Arabia.
Laboratoire de Caractérisations, Applications et Modélisations des Matériaux, Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis 2092, Tunisia.
Bioorg Chem. 2021 Sep;114:105099. doi: 10.1016/j.bioorg.2021.105099. Epub 2021 Jun 17.
A series of the title curcuminoids with structural variance in the heteroatom of the cycloalkanone and the p-substituents of the phenyl rings were tested for their activities against Leishmania major and Toxoplasma gondii parasites. The majority of them showed high activities against both parasite forms with EC values in the sub-micromolar concentration range. Bis(p-pentafluorothio)-substituted 3,5-di[(E)-benzylidene]piperidin-4-one 1b was not just noticeable antiparasitic, but also exhibited a considerable selectivity for L. major promastigotes over normal Vero cells. While derivatives differing only in the p-phenyl substituents being CF or SF showed similar antiparasitic activities, the cyclic ketone hub was more decisive both for the anti-parasitic activities and the selectivities for the parasites vs. normal cells. QSAR calculations confirmed the observed structure-activity relations and suggested structural variations for a further improvement of the antiparasitic activity. Docking studies based on DFT calculations revealed L. major pteridine reductase 1 as a likely molecular target protein of the title compounds.
一系列标题姜黄素类似物在环己酮的杂原子和苯基环的 p-取代基方面具有结构差异，它们的活性被测试了对利什曼原虫和刚地弓形虫寄生虫的活性。它们中的大多数对两种寄生虫形式都表现出很高的活性，EC 值在亚微米摩尔浓度范围内。双（p-五氟硫代）取代的 3,5-二[(E)-亚苄基]哌啶-4-酮 1b 不仅具有显著的抗寄生虫活性，而且对利什曼原虫前鞭毛体相对于正常 Vero 细胞也表现出相当大的选择性。虽然在 p-苯基取代基上仅存在 CF 或 SF 的衍生物表现出相似的抗寄生虫活性，但环状酮枢纽对寄生虫与正常细胞的抗寄生虫活性和选择性都更为决定性。QSAR 计算证实了观察到的结构-活性关系，并提出了进一步提高抗寄生虫活性的结构变化。基于 DFT 计算的对接研究表明，利什曼原虫蝶啶还原酶 1 是标题化合物的可能的分子靶蛋白。
