Dunay Ildiko R, Chan Wing Chi, Haynes Richard K, Sibley L David
Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Antimicrob Agents Chemother. 2009 Oct;53(10):4450-6. doi: 10.1128/AAC.00502-09. Epub 2009 Jul 27.
Immunocompromised patients are at risk of developing toxoplasmosis, and although chemotherapy is available, standard treatments are often complicated by severe side effects. Artemisinin is a new highly potent antimalarial drug that has activity against Toxoplasma gondii in vitro. However, artemisinin derivatives have previously been ineffective in vivo using a rat model of toxoplasmosis. In the present study, the efficacy of several new artemisinin derivates was investigated for treatment of mice infected with the parasite Toxoplasma gondii. Artemiside and artemisone displayed better inhibition than either artemisinin or artesunate against the parasite in vitro. Artemiside and artemisone treatment controlled parasite replication in vivo, and mice survived the acute infection. In a murine model of reactivated toxoplasmosis, both drugs increased survival, although artemiside was more effective. These results indicate that these newer derivatives of artemisinin may have potential for treatment of toxoplasmosis.
免疫功能低下的患者有患弓形虫病的风险,尽管有化疗方法可用,但标准治疗常常因严重的副作用而变得复杂。青蒿素是一种新型高效抗疟药物,在体外对刚地弓形虫有活性。然而,在先前使用弓形虫病大鼠模型的研究中,青蒿素衍生物在体内无效。在本研究中,研究了几种新型青蒿素衍生物对感染寄生虫刚地弓形虫的小鼠的治疗效果。在体外,青蒿琥酯和青蒿酮对该寄生虫的抑制作用比青蒿素或青蒿琥酯更好。青蒿琥酯和青蒿酮治疗可在体内控制寄生虫复制,并且小鼠在急性感染中存活下来。在弓形虫病再激活的小鼠模型中,两种药物都提高了生存率,尽管青蒿琥酯更有效。这些结果表明,这些新型青蒿素衍生物可能具有治疗弓形虫病的潜力。