STRUCTURE-BASED DESIGN OF ANTIPARASITIC AGENTS

开发一系列相关寄生虫病的新化学疗法，即利什曼病、恰加斯病和疟疾。全世界有数百万人受到这些疾病的影响。由于出现了耐药性，目前对它们的治疗并不令人满意。利用分子模拟和组合化学的方法，在前导PS28的基础上，设计并合成了大肠弯曲杆菌的非肽类抑制剂文库、壳聚糖羟乙胺异构酶抑制剂文库、恶性痛的尿素类抑制剂文库。由于这些酶是同源的，将对每个抑制剂文库进行所有三种酶的检测，以确定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.