POTENTIATION OF ANTIMALARIAL OXIDANT DRUGS

描述（改编自申请人的摘要）：在全球范围内 据估计，原生动物寄生虫恶性疟原虫（Plasmodium falciparum） 每年超过8亿例疟疾病例。在这个数字中 大约1.5亿人患有严重疾病， 每年由恶性疟原虫引起的死亡人数估计为2 万人们普遍认为，全球疟疾负担 在未来的几年里，由于不断出现 恶性疟原虫耐药菌株的增加， 国际旅行。因此，迫切需要新的药物 以及在药物滥用领域更有效地使用现有药物 抵抗尚未成为普遍现象。INTERLAB的研究人员 最近发现抗疟疾化合物 与某些专有试剂结合使用。 协同作用导致抗疟活性增强至少300 折这些化合物的存在并不明显影响 正常哺乳动物细胞在体外的生长和分化， 可能代表了对治疗的深远影响的观察结果， 疟疾由于拟议的行动地点导致这一点， 抗疟协同作用，这一观察结果也可能具有 在控制由原生动物寄生虫引起的其它疾病中的应用。 因此，肺孢子虫和隐孢子虫引起的感染， 免疫功能低下的艾滋病患者的临床相关性，可能是 通过应用这种药物协同作用更容易控制。 在第一阶段的应用中，他们将为此奠定基础。 观察抗疟药物的协同作用，包括 恶性疟原虫的多重耐药菌株，并将启动 旨在确定协同作用机制的研究 反应

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.