AIDS OPPORTUNISTIC INFECTIONS DRUG DESIGN

卡氏肺孢子虫肺炎(PCP)是卡氏肺孢子虫肺炎的主要杀手 艾滋病患者。同样，弓形虫，一种普遍存在的 寄生原生动物，在 艾滋病患者。目前对卡氏肺孢子虫和T。 弓形虫感染通常会产生严重的副作用，导致 停止治疗。人们普遍认为，新药具有 迫切需要新的作用机制来治疗 五氯联苯和弓形虫病。建立在先前药物化学的基础上 研究，我们已经启动了两个基于结构的药物设计计划 改进的弓形虫次黄嘌呤-鸟嘌呤抑制剂的研制 磷酸核糖转移酶(HGPRT)，弓形虫二氢叶酸 还原酶胸苷合成酶(DHFR-TS)和卡氏肺孢子虫DHFR。

Pneumocystis carinii pneumonia (PCP) is the leading killer of patients with AIDS. Similarly, Toxomplasma gondii, a pervasive parasitic protozoan, causes significant morbidity and mortality among AIDS patients. Current treatment regimens for both P. carinii and T. gondii infections often produce severe side effects, leading to the cessation of therapy. It is widely recognized that new drugs having novel mechanisms of action are urgently needed for the treatment of PCP and toxoplasmosis. Building upon prior medicinal chemistry research, we have initiated two structure-based drug design programs to make improved inhibitors of T. gondii hypoxanthine-guanine phosphoribosyltransferase (HGPRT), T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS) and P. carinii DHFR.