Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C₂ symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (K_i, 1.93 ± 0.29 µM for Plm II; K_i, 1.99 ± 0.05 µM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (K_i, 0.84 ± 0.08 µM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC₅₀, 2.27 ± 0.95 µM for 10f; IC₅₀, 3.11 ± 0.65 µM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC₅₀ value of 1.35 ± 0.85 µM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.

疟疾，特别是在流行国家，仍然是对人类健康的威胁，是热带和亚热带地区致死的主要原因。在这里，我们探索了新的C ₂对称羟乙胺类似物作为体外培养中恶性疟原虫（P. falciparum ; 3D7）的潜在抑制剂。还对所有列出的化合物进行了针对关键药物靶标，恶性疟原虫消化液中发现的纤溶酶II（Plm II）和IV（Plm IV）的评估。类似物10f对Plm II和Plm IV酶均显示抑制活性（K _i，Plm II为1.93±0.29 µM； K _i，对于Plm IV，为1.99±0.05 µM）。在所有这些类似物中，化合物10g选择性抑制Plm IV的活性（K _i，0.84±0.08 µM）。在体外筛选试验中，生长的抑制恶性疟原虫由两个类似物（IC ₅₀，2.27±0.95μM为10F ; IC ₅₀，3.11±0.65μM为10克）中显示的标记的杀灭作用。具有IC _50的类似物12c对恶性疟原虫具有显着的生长抑制作用数值为1.35±0.85 µM，但是对任何一种Plms均没有抑制活性。溶血分析表明活性化合物选择性抑制了寄生虫的生长。此外，评估了有效的类似物（10f和12c）对哺乳动物HepG2和vero细胞的细胞毒性。注意到表明它们的不良毒性的两个类似物的选择性指数（SI）值均大于10。本研究表明这些类似物是推定的前导结构，并且可能对开发新药物分子起关键作用。