POTENTIATION OF ANTIMALARIAL OXIDANT DRUGS

描述(改编自申请者摘要)：全球范围 据估计，原生动物寄生虫恶性疟原虫在 每年超过8亿疟疾病例。这个数字中的 大约1.5亿人患上了严重的疾病 每年由恶性疟原虫引致的死亡人数估计为2。 百万美元。人们普遍认为，全球范围内疟疾的负担 在未来几年将会增加，因为不断出现的 恶性疟原虫耐药株和显著增加 国际旅行。因此，迫切需要新药。 以及在以下领域更有效地使用现有药物 抗药性尚未变得普遍。InterLab的调查人员已经 最近发现一种显著的抗疟疾化合物之间的协同作用 氧化剂类与某些专有试剂相结合。 协同作用导致抗疟疾活性增强至少300 收牌。这些化合物的存在并不明显地影响 正常哺乳动物细胞在体外的生长和分化 可能代表了一项对治疗该病影响深远的观察 疟疾。因为拟议的行动地点导致了这一点 抗疟疾的协同作用，这一观察结果也很可能会 在原生动物寄生虫引起的其他疾病防治中的应用。 因此，由肺孢子虫和隐孢子虫引起的感染，特别是 免疫功能低下的艾滋病患者的临床相关性可能是 更容易通过应用这种药物协同作用进行控制。 在此阶段I应用程序中，他们将为此奠定基础 抗疟疾药物协同作用的观察 恶性疟原虫多重耐药株，并将启动 旨在确定协同作用的机制的研究 回应。

DESCRIPTION (Adapted from the Applicant's Abstract): On a global scale the protozoan parasite Plasmodium falciparum is estimated to cause in excess of 800 million cases of malaria per year. Of this number approximately 150 million individuals develop serious disease with the annual number of deaths caused by P. falciparum is estimated to be 2 million. It is generally believed that the worldwide burden of malaria will increase in the upcoming years because of the continual emergence of drug-resistance strains of P. falciparum and the significant increase in international travel. As a result there is a urgent need for new drugs and more efficient use of existing drugs in areas in which drug resistance has yet to become prevalent. Investigators at INTERLAB have recently discovered a significant synergy between antimalarial compounds of the oxidant class in combination with certain proprietary reagents. The synergy leads to potentiation of antimalarial activity at least 300 fold. The presence of these compounds does not apparently influence the growth and differentiation of normal mammalian cells in vitro and thus may represent an observation of far reaching impact for treatment of malaria. Because of the proposed site of action leading to this antimalarial synergy, it is also likely that this observation will have application in the control of other disease caused by protozoan parasites. Thus, infections caused by Pneumocystis and Cryptosporidium, of special clinical relevance in immunocompromised patients with the AIDS, may be controlled more readily by application of this drug synergy. In this Phase I application they will establish the basis for this observation of antimalarial drug synergy including the response of multiple-drug resistant strains of P. falciparum and will initiate studies designed to determine mechanisms responsible for the synergistic response.