Peroxides for Chemotherapy of Malaria and Cancer

描述(申请人提供)：迫切需要新药对疟疾和癌症等广泛传播的人类疾病进行有效和无毒的化疗。我们正在将化学见解和合成技术与体外生物测试相结合，然后对最有希望的新化学实体，在体内建立有效性和安全性。这种跨学科的研究是我们在霍普金斯大学为疟疾和癌症的化疗候选新药的实际临床前开发项目的特点。基于我们在抗感染和抗癌过氧化物质，如天然三氧六环青蒿素及其一些晚餐方面的良好机理和合成进展，我们提出了未来五年的以下五个研究目标：(1)设计、制备和评价新的、结构简单、易于制备、廉价、有效和安全的新的、结构简单、易于制备、价格低廉、有效和安全的(A)单体合成内氧化物；(2)设计、制备和评价由二氢青蒿素醋酸酯制备的新的、有效的和安全的半合成二聚体；(B)青蒿素-9-烯-10-醛(3)，以确定我们最有希望的二聚内氧化物和三氧六环的分子作用机理。作为合成和药物化学家，我们在分子寄生虫学和肿瘤学方面取得了根本性的进展，特别是在抗疟疾和抗癌候选药物的作用机制方面，帮助改善了易于制备和相对便宜的新过氧物的治疗方面。

DESCRIPTION (provided by applicant): 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 and safety. This interdisciplinary research characterizes our program at Hopkins for practical preclincial development of new drug candidates for chemotherapy of malaria and cancer. Based on our good mechanistic and synthetic progress with anti-infective and anticancer peroxides like the natural trioxane artemisinin and some of its dinners, we propose the following five research goals for the next five years: (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 prepared (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 improved therapeutic aspects of easily prepared and relatively inexpensive new peroxides as antimalarial and anticancer drug candidates.