Federal University of Pernambuco (UFPE), Department of Antibiotics, 50670-901, Recife, PE, Brazil.
University of International Integration of Afro-Brazilian Lusophony (UNILAB), 62790-970, Redenção, CE, Brazil.
Exp Parasitol. 2023 May;248:108498. doi: 10.1016/j.exppara.2023.108498. Epub 2023 Mar 11.
In this work, 13 thiosemicarbazones (1a - m) and 16 thiazoles (2a - p) were obtained, which were properly characterized by spectroscopic and spectrometric techniques. The pharmacokinetic properties obtained in silico revealed that the derivatives are in accordance with the parameters established by lipinski and veber, showing that such compounds have good bioavailability or permeability when administered orally. In assays of antioxidant activity, thiosemicarbazones showed moderate to high antioxidant potential when compared to thiazoles. In addition, they were able to interact with albumin and DNA. Screening assays to assess the toxicity of compounds to mammalian cells revealed that thiosemicarbazones were less toxic when compared to thiazoles. In relation to in vitro antiparasitic activity, thiosemicarbazones and thiazoles showed cytotoxic potential against the parasites Leishmania amazonensis and Trypanosoma cruzi. Among the compounds, 1b, 1j and 2l stood out, showing inhibition potential for the amastigote forms of the two parasites. As for the in vitro antimalarial activity, thiosemicarbazones did not inhibit Plasmodium falciparum growth. In contrast, thiazoles promoted growth inhibition. This study shows in a preliminary way that the synthesized compounds have antiparasitic potential in vitro.
在这项工作中,得到了 13 个硫代氨基甲脒(1a-m)和 16 个噻唑(2a-p),它们通过光谱和光谱技术得到了适当的表征。通过计算机获得的药代动力学特性表明,这些衍生物符合 Lipinski 和 Veber 建立的参数,表明这些化合物在口服给药时具有良好的生物利用度或通透性。在抗氧化活性测定中,与噻唑相比,硫代氨基甲脒显示出中等至高的抗氧化潜力。此外,它们能够与白蛋白和 DNA 相互作用。用于评估化合物对哺乳动物细胞毒性的筛选试验表明,与噻唑相比,硫代氨基甲脒的毒性较低。关于体外抗寄生虫活性,硫代氨基甲脒和噻唑对寄生虫利什曼原虫和克氏锥虫表现出细胞毒性潜力。在这些化合物中,1b、1j 和 2l 表现出对两种寄生虫的无鞭毛体形式的抑制潜力。至于体外抗疟原虫活性,硫代氨基甲脒不能抑制恶性疟原虫的生长。相反,噻唑促进了生长抑制。这项研究初步表明,合成的化合物具有体外抗寄生虫潜力。