Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70–73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70–73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC₅₀s < 0.28 μM), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC₅₀s < 0.7 μM for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.

设计，合成，结构-活性关系，细胞毒性研究，计算机模拟药物，遗传毒性筛选以及新的1-芳基-3-取代丙醇衍生物的体内研究导致鉴定了九种具有良好体外前景的化合物（55，56，61，64，66，和70 - 73）和体内（66和72）抗疟疾型材针对恶性疟原虫和疟原虫。化合物55，56，61，64，66和70 - 73表现出强效的抗疟原虫活性对耐氯喹株FCR-3（IC _50个小号<0.28μM），和化合物55，56，64，70，71，和72显示出有效的生物活性的氯喹敏感和多药耐药菌株（对于3D7，D6，FCR-3和C235，IC ₅₀ s <0.7μM）。所有这些化合物都具有适当的药物相似性和适当的选择性指数（77 <SI <184），并且缺乏遗传毒性。体内在小鼠模型中进行的功效测试表明，化合物66和72是有前途的候选物，因为它们分别显示出96.4％和80.4％的显着降低。进行了其他研究，例如肝分期和孢子形成抑制，恶性疟原虫热休克蛋白90的靶点探索，免疫脂质体的靶点递送以及对映异构体表征，这些研究强有力地强化了1-芳基-3-取代的丙醇衍生物作为有希望的抗疟药的假说。化合物。