a BIOINOVAR - Biotechnology Laboratories: Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil .
b Faculdade São Francisco de Barreiras (FASB) , Barreiras , BA , Brazil .
J Enzyme Inhib Med Chem. 2016 Dec;31(6):964-73. doi: 10.3109/14756366.2015.1077330. Epub 2015 Aug 31.
This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases.
这项工作描述了两种含羟肟酸衍生物的抗锥虫活性，它们在芳香环上带有邻乙氧基（HAD1）和对乙氧基（HAD2）取代基，与异恶唑啉环相连。HAD1 和 HAD2 可显著减少细胞内寄生虫的数量，并因此对寄生虫的繁殖具有活性。用这些化合物处理心肌细胞和巨噬细胞，细胞活力没有明显下降。用 HAD1 的 IC50 值处理感染 Trypanosoma cruzi 的心肌细胞或巨噬细胞后，超微结构的改变显示出对变形体的改变，显示出最初的损伤，表现为基体的肿胀。这很好地表明了药物穿透宿主细胞膜的能力及其对寄生虫靶标的选择性。两种化合物 HAD1 和 2 都能够减少半胱氨酸肽酶并降低金属肽酶的活性。
