摘要
Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endoperoxide bridge to generate free radicals followed by such membrane damages as lipid peroxidation and protein denaturation. The interaction of the endoperoxides with heme also enhances heme-induced membrane toxicity by way of stimulating the redox activity of heme and preventing its polymerization to chemically inert pigment. Moreover, the drug-derivative radicals may disturb the parasites prooxidant-antioxidant balance, thereby sensitizing them to subsequent lethal damages of endogenous and exogenous oxidants increase. The free radicals-mediated mode of action of the endoperoxides may be used to explain such phenomena as sex difference and developmental stage difference in susceptibility to the endoperoxides as well as their slow schistosome killing.
Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endoperoxide bridge to generate free radicals followed by such membrane damages as lipid peroxidation and protein denaturation. The interaction of the endoperoxides with heme also enhances heme-induced membrane toxicity by way of stimulating the redox activity of heme and preventing its polymerization to chemically inert pigment. Moreover, the drug-derivative radicals may disturb the parasites prooxidant-antioxidant balance, thereby sensitizing them to subsequent lethal damages of endogenous and exogenous oxidants increase. The free radicals-mediated mode of action of the endoperoxides may be used to explain such phenomena as sex difference and developmental stage difference in susceptibility to the endoperoxides as well as their slow schistosome killing.
出处
《中国热带医学》
CAS
2003年第3期391-394,共4页
China Tropical Medicine
基金
青蒿素科技基金资助
关键词
自由基
调节
青蒿素类药物
抗血吸虫作用
Artemisinin-typed compounds, Free radicals, Heme, Schistosome, Membrane damage, Antioxidant system.
