Artemisinin-ferrocene conjugates incorporating a 1,2-disubstituted ferrocene analogous to that embedded in ferroquine but attached via a piperazine linker to C10 of the artemisinin were prepared from the piperazine artemisinin derivative, and activities were evaluated against asexual blood stages of chloroquine (CQ) sensitive NF54 and CQ resistant K1 and W2 strains of Plasmodium falciparum (Pf). The most active was the morpholino derivative 5 with IC₅₀ of 0.86 nM against Pf K1 and 1.4 nM against Pf W2. The resistance indices were superior to those of current clinical artemisinins. Notably, the compounds were active against Pf NF54 early and late blood stage gametocytes – these exerted >86% inhibition at 1 µM against both stages; they are thus appreciably more active than methylene blue (∼57% inhibition at 1 µM) against late stage gametocytes. The data portends transmission blocking activity. Cytotoxicity was determined against human embryonic kidney cells (Hek293), while human malignant melanoma cells (A375) were used to assess their antitumor activity.

青蒿素-二茂铁偶联物包含与嵌入二茂铁中的二茂铁类似但通过哌嗪接头连接到青蒿素的 C10 的1,2-二茂铁偶联物是从哌嗪青蒿素衍生物制备的，并针对氯喹 (CQ) 的无性血阶段评估了活性敏感的 NF54 和 CQ 抗性 K1 和 W2恶性疟原虫菌株（Pf）。最活跃的是吗啉衍生物5，其对Pf K1 的IC ₅₀为 0.86 nM，对Pf W2 的IC ₅₀为1.4 nM 。抗性指标优于目前临床青蒿素的抗性指标。值得注意的是，这些化合物对Pf具有活性NF54 早期和晚期血液配子体——这些在 1 µM 时对这两个阶段产生 >86% 的抑制；因此，它们对晚期配子细胞的活性明显高于亚甲蓝（在 1 µM 时抑制约 57%）。该数据预示着传输阻塞活动。确定了对人胚胎肾细胞 (Hek293) 的细胞毒性，而人恶性黑色素瘤细胞 (A375) 用于评估它们的抗肿瘤活性。