Peroxides for Chemotherapy of Malaria and Cancer

对广泛传播的人类疾病进行有效和无毒的化疗迫切需要新药 比如疟疾和癌症。我们正在将化学见解和合成技术与体外生物测试相结合 然后，对于最有前景的新化学实体，在体内建立有效性和安全性。这 跨学科研究是我们在霍普金斯大学的项目的特点，我们的项目旨在为新的 治疗疟疾和癌症的候选药物。 基于我们良好的抗感染和抗癌过氧化物类的机械和合成进展 天然三氧六环青蒿素及其部分膳食，我们提出了以下五个研究目标 未来五年： (1)设计、准备和评估新的、结构简单、容易准备、廉价、有效和安全的 (A)单体合成内过氧物； (B)二聚合成内过氧物 (2)设计、制备和评价新的、有效的、安全的半合成二聚体。 (A)乙酸双氢青蒿素； (B)青蒿素-9-烯-10-醛 (3)确定我们最有希望的二聚内过氧物的分子作用机制和 三氧六环。 作为合成和药物化学家，我们处于独特的地位，可以在以下方面取得根本性进展 分子寄生虫学和肿瘤学，特别是关于作用机制的帮助改善了治疗 易制备和相对廉价的抗疟疾和抗癌新过氧物的方面 候选人。

New drugs are urgently needed for effective and non-toxic 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 nnd safety. This interdisciplinary research characterizes our program at Hopkins for practical preclincial development of new drug candidates for chemotherapy of malaria andcancer. Based on our good mechanistic and synthetic progresswith anti-infective and anticancerperoxides like the natural trioxane artemisinin and some of its dinners, we propose the following five research goals for the next fiveyears: (1) to design, prepare, and evaluate new, structurally simple, easily prepared, inexpensive, potent and safe (a) monomeric synthetic endoperoxides; (b) dimeric synthetic endoperoxides (2) to design, prepare, and evaluate new, potent, and safe semi-synthetic dimers jrepared (a) from dihydroartemisinin acetate; (b) from artemisinin-9-en-10-aldehyde (3) to determine the molecular mechanism of action of our most promising dimeric endoperoxides and trioxanes. 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 aid improvedtherajoeutic aspects of easily prepared and relatively inexpensive new peroxides as antimalarial and anticancerdr jg candidates.