TRIOXANES FOR CHEMOTHERAPY OF MALARIA AND CANCER

描述：由于疟疾和癌症在许多地区的高发病率， 有效和安全的新的化学疗法，这些人类疾病的世界， 迫切需要。为了开发这种实用的新化疗药物， 我们正在将化学洞察力和合成技能与生物测试相结合， 最初在体外，然后在体内，以确定功效和安全性。这 基础化学和药理学研究与实践相结合 新药候选药物的临床前开发突出了我们正在进行的 霍普金斯的三恶烷用于疟疾化疗的研究项目， 癌 基于我们已经产生的关于分子的基本新知识， 有效的抗感染过氧化物的作用机制，如天然的 三恶烷青蒿素，我们提出以下五个不同的研究目标， 未来五年：（1）设计，准备和评估结构简单， 廉价、有效和安全的下一代抗疟疾三恶烷;（2） 设计、制备和评价作为新型抗感染剂的二缩二甲醛过氧化物， 特别是抗肿瘤候选药物;（4）发明新的合成方法， 高效廉价构建化疗抗疟药物 （5）设计、制备和评价新的抗疟内过氧化物 过氧化物基团被其它杂原子取代的类似物。 作为药物化学家，我们处于一个独特的位置，可以在以下方面取得根本性的进展： 分子寄生虫学，特别是关于作用机制和未经证实的 治疗方面的容易制备和相对便宜的新的 内过氧化物抗疟疾和抗肿瘤药物。

DESCRIPTION: Because of the high incidence of malaria and cancer in many parts of the world, effective and safe new chemotherapies of these human diseases are urgently needed. Toward developing such practical new chemotherapeutic drugs, we are blending chemical insight and synthesis skills with biological testing initially in vitro and then in vivo to establish efficacy and safety. This blending of fundamental chemistry and pharmacology research with practical pre-clinical development of new drugs candidates highlights our ongoing research program at Hopkins on trioxanes for chemotherapy of malaria and cancer. Based on the fundamental new knowledge we have generated about the molecular mechanism of action of potent anti-infective peroxides like the natural trioxane artemisinin, we propose the following, five diverse research goals for the next five years: (1) to design, prepare and evaluate structurally simple, inexpensive, potent, and safe next-generation antimalarial trioxanes; (2) to design, prepare and evaluate dimetric peroxides as new anti-infective and especially antitumor drug candidates; (4) to invent new synthetic methods for efficiently and inexpensive constructing chemotherapeutic antimalarial peroxides; (5) to design, prepare and evaluate new antimalarial endoperoxide analogs in which the peroxide groups is replaced by other heteroatoms. As medicinal chemists, we are a unique position to make fundamental advances in molecular parasitology specifically concerning mechanism of action and unproved therapeutic aspects of easily prepared and relatively inexpensive new endoperoxide antimalarial and antitumor drugs.