STRUCTURE-BASED DESIGN OF ANTIPARASITIC AGENTS

为一系列相关的寄生虫病，即利什曼病、恰加斯病和疟疾，开发新的化学疗法。全世界有数百万人受到这些疾病的影响。由于出现耐药性，目前对他们的治疗并不令人满意。利用分子模拟和组合化学的方法，设计合成了基于前人先导物PS28的L. major cpB非肽抑制剂文库、cruzain羟乙胺同分异构体抑制剂文库、falcipain尿素抑制剂文库。由于这些酶是同源的，每个抑制剂文库将对所有三种酶进行检测，以检测它们抑制寄生虫生长的能力以及它们的毒性。

Develop new chemotherapy for a series of related parsitic diseases, namely leishmaniasis, Chagas disease and malaria. Millions of people worldwide are influenced by these diseases. Current therapy for them is unsatisfactory due to the emergence of drug resistance. With the aid of molecular modeling and combinatorial chemistry, libraries of nonpeptide inhibitors of L. major cpB based on a previous lead PS28, a library of hydroxyethylamine isostere inhibitors of cruzain, a library of urea inhibitors of falcipain will be designed and synthesized. As these enzymes are homologous, each library of inhibitors will be assayed for all three enzymes, for their ability to inhibit parasite growth as well as their toxicity.