A series of new quinazolinedione derivatives have been readily synthesized and evaluated for their in vitro antiplasmodial growth inhibition activity. Most of the compounds inhibited P. falciparum FcB1 strain in the low to medium micromolar concentration. The 2-ethoxy 8ag’, 2-trifluoromethoxy 8ai’ and 4-fluoro-2-methoxy 8ak’ showed the best inhibitory activity with EC₅₀ values around 5 µM and were non-toxic to the primary human fibroblast cell line AB943. However, these compounds were less potent than the original hit MMV665916, which showed remarkable growth inhibition with EC₅₀ value of 0.4 µM and presented the highest selectivity index (SI > 250). In addition, a novel approach for determining the docking poses of these quinazolinedione derivatives with their potential protein target, the P. falciparum farnesyltransferase PfFT, was investigated.

一系列新的喹唑啉二酮衍生物很容易合成，并评估了它们的体外抗疟原虫生长抑制活性。大多数化合物在低至中等微摩尔浓度下抑制恶性疟原虫FcB1菌株。2-乙氧基8ag'、2-三氟甲氧基8ai'和4-氟-2-甲氧基8ak'显示出最好的抑制活性，EC ₅₀值约为5 µM，并且对原代人成纤维细胞系AB943无毒。然而，这些化合物的效力不如最初的热门 MMV665916，后者显示出显着的 EC _{50生长抑制作用}值为 0.4 µM 并呈现最高的选择性指数 (SI > 250)。此外，研究了一种确定这些喹唑啉二酮衍生物与其潜在蛋白质靶标——恶性疟原虫法尼基转移酶Pf FT 的对接姿势的新方法。