Peroxides for Chemotherapy of Malaria and Cancer

对于广泛存在的人类疾病， 疟疾和癌症。我们将化学见解和合成技能与体外生物测试相结合， 然后，对于最有前途的新化学实体，在体内建立疗效和安全性。这个跨学科 研究的特点是我们的计划在霍普金斯的实际临床前发展的新药候选人， 疟疾和癌症的化疗。我们正与工业界合作， 沿着药物开发的道路，在我国抗感染药物和 抗癌过氧化物如天然三恶烷青蒿素和它的一些二聚体，我们提出以下建议 未来五年的研究目标： 1..继续设计，制备和评估新的，结构简单，易于制备，廉价，有效 和安全的二聚合成内过氧化物; 2.继续在开发安全和选择性的新型半合成三恶烷方面进行优化， 抗疟疾和抗癌活性， (a)（B）青蒿素-9-烯-10-醛; 3.继续探索我们最有前途的过氧化物的抗疟和抗癌作用机制。 作为合成和药物化学家，我们处于独特的地位，在分子生物学领域取得根本性进展。 寄生虫学和肿瘤学，特别是关于作用机制和改进的治疗方面， 容易制备且相对便宜的新过氧化物作为抗疟疾和抗癌药物候选物。 NIH R37-AI-34885 2006-2009年的进展和2011-2015年的计划详述如下 页面. 相关性（参见说明）： 开发安全有效的抗疟和抗癌过氧化物药物以改善人类健康。

New drugs are urgently needed for safe and effective chemotherapy of widespread human diseases like malaria and cancer. We are blending chemical insights and synthesis skills with biological testing in vitro and then, for the most promising new chemical entities, in vivo to establish efficacy and safety. This interdisciplinary research characterizes our program at Hopkins for practical preclincial development of new drug candidates for chemotherapy of malaria and cancer. We are partnering with industry to move one or two of our lead peroxides along the drug development path. Based on our good mechanistic and synthetic progress with anti-infective and anticancer peroxides like the natural trioxane artemlslnin and some of its dimers, we propose the following research goals for the next flve years:. 1.. To continue to design, prepare, and evaluate new, structurally simple, easily prepared, inexpensive, potent and safe dimeric synthetic endoperoxides; 2. To continue lead optimization in developing safe and selective new semi-synthetic trioxanes having both antimalarial and anticancer activities, starting with (a) dihydroartemisinin acetate (b) artemisinin-9-en-lO-aldehyde; 3. To continue exploring mechanism of antimalarial and anticancer action of our most promising peroxides. As synthetic and medicinal chemists, we are in a unique position to make fundamental advances in molecular parasitology and oncology specifically concerning mechanism of action and improved therapeutic aspects of easily prepared and relatively inexpensive new peroxides as antimalarial and anticancer drug candidates. Progress covering 2006-2009 on NIH R37-AI-34885 and plans for 2011-2015 are detailed on the following pages. RELEVANCE (See instructions): Development of safe and efficacious antimalarial and anticancer peroxide drugs for improving human health.