Laboratory of Medicinal Chemistry, Center of Interdisciplinary Research on Medicines (CIRM), University of Liege, 4000 Liège, Belgium.
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, 4000 Liège, Belgium.
Molecules. 2023 Jun 2;28(11):4516. doi: 10.3390/molecules28114516.
Malaria is an infectious disease caused by a genus parasite that remains the most widespread parasitosis. The spread of clones that are increasingly resistant to antimalarial molecules is a serious public health problem for underdeveloped countries. Therefore, the search for new therapeutic approaches is necessary. For example, one strategy could consist of studying the redox process involved in the development of the parasite. Regarding potential drug candidates, ellagic acid is widely studied due to its antioxidant and parasite-inhibiting properties. However, its low oral bioavailability remains a concern and has led to pharmacomodulation and the synthesis of new polyphenolic compounds to improve antimalarial activity. This work aimed at investigating the modulatory effect of ellagic acid and its analogues on the redox activity of neutrophils and myeloperoxidase involved in malaria. Overall, the compounds show an inhibitory effect on free radicals as well as on the enzyme horseradish peroxidase- and myeloperoxidase (HRP/MPO)-catalyzed oxidation of substrates (L-012 and Amplex Red). Similar results are obtained with reactive oxygen species (ROS) produced by phorbol 12-mystate acetate (PMA)-activated neutrophils. The efficiency of ellagic acid analogues will be discussed in terms of structure-activity relationships.
疟疾是一种由寄生虫属引起的传染病，仍然是最广泛传播的寄生虫病。对青蒿素分子越来越耐药的克隆的传播，是欠发达国家面临的一个严重的公共卫生问题。因此，有必要寻找新的治疗方法。例如，一种策略可以是研究参与寄生虫发育的氧化还原过程。关于潜在的药物候选物，由于其抗氧化和抑制寄生虫的特性，鞣花酸受到了广泛的研究。然而，其口服生物利用度低仍然是一个问题，这导致了对其进行药物修饰和合成新的多酚化合物以提高抗疟活性。这项工作旨在研究鞣花酸及其类似物对参与疟疾的中性粒细胞和髓过氧化物酶的氧化还原活性的调节作用。总的来说，这些化合物对自由基以及辣根过氧化物酶和髓过氧化物酶（HRP/MPO）催化的底物（L-012 和 Amplex Red）氧化具有抑制作用。用佛波醇 12-肉豆蔻酸酯（PMA）激活的中性粒细胞产生的活性氧（ROS）也得到了类似的结果。鞣花酸类似物的效率将根据构效关系进行讨论。
