Sharma Arun
Indian Council of Medical Research, National Institute of Malaria Research, 22 Sham Nath Marg, Delhi 110 054, India.
Curr Opin Investig Drugs. 2007 Aug;8(8):642-52.
The current limitations of malaria vaccine development, and the emergence and spread of insecticide-resistant vectors and drug-resistant parasites are major causes behind the re-emergence and severity of a worldwide malaria problem. A potential new target for antimalarial chemotherapy includes the malarial proteases that are required for erythrocytic invasion, egress and degradation of hemoglobin by parasites for its survival. Protease inhibitors must be highly potent and specific for parasite proteases to be recognized as biological tools. Screening, synthesis and evaluation studies have identified non-peptide derivatives that are able to kill parasites in vitro via protease inhibition. This review summarizes experimental evidence to support the rational design and development of protease inhibitors as potential new antimalarial drugs.
疟疾疫苗研发目前存在的局限性，以及抗杀虫剂媒介和耐药寄生虫的出现与传播，是全球疟疾问题再度出现并加剧的主要原因。抗疟化疗的一个潜在新靶点包括疟原虫蛋白酶，这些蛋白酶是疟原虫侵入红细胞、逸出红细胞以及降解血红蛋白以供自身生存所必需的。蛋白酶抑制剂必须对寄生虫蛋白酶具有高效力和特异性，才能被视为生物学工具。筛选、合成和评估研究已鉴定出能够通过抑制蛋白酶在体外杀死寄生虫的非肽衍生物。本综述总结了实验证据，以支持将蛋白酶抑制剂合理设计和开发为潜在的新型抗疟药物。
