Anti-Parasite and Cytotoxic Activities of Chloro and Bromo L-Tyrosine Derivatives

A series of twenty-one L-tyrosine derivatives with modifications in the halogenation pattern of the aromatic ring and different degree of methylations on the amine and phenolic hydroxyl groups were synthesized. The structures of all the intermediates and target compounds were confirmed unambiguous by spectroscopy analysis. Additionally, all compounds were evaluated against Plasmodium falciparum and Leishmania panamensis parasites between 20-702 µg mL-1. The cytotoxic evaluation was done to determine the selectivity index for each compound. Six compounds had the lower EC50 (effective concentration 50) against L. panamensis. One of these compounds was the most active with an EC50 at 24.13 µg mL-1 (76.07 µM). All derivatives showed no significant activity against P. falciparum and no compound has in vitro antifungal activity at 500 µg mL-1.

本研究合成了21种L-酪氨酸衍生物，此类衍生物的芳香环卤代模式存在差异，且胺基与酚羟基的甲基化程度各不相同。通过光谱分析对所有中间体及目标化合物的结构进行了明确确证。此外，在20~702 μg·mL⁻¹的浓度范围内，对所有化合物开展了抗恶性疟原虫（Plasmodium falciparum）与巴拿马利什曼原虫（Leishmania panamensis）的体外活性评价。同时进行细胞毒性评价，以测定各化合物的选择性指数。其中6种化合物针对巴拿马利什曼原虫的半最大效应浓度（EC50，effective concentration 50）更低。该6种化合物中活性最强的一种，其EC50值为24.13 μg·mL⁻¹（76.07 μM）。所有衍生物对恶性疟原虫均未表现出显著活性，且在500 μg·mL⁻¹的浓度下未检测到体外抗真菌活性。