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。由于耐药性的出现，目前对它们的治疗不能令人满意。 在分子模拟和组合化学的帮助下，建立了乳酸杆菌非肽抑制剂库。major cpB基于先前的先导PS28，cruzain的羟乙胺等排体抑制剂库，将设计和合成镰状蛋白酶的尿素抑制剂库。由于这些酶是同源的，因此将针对所有三种酶测定每个抑制剂文库抑制寄生虫生长的能力以及毒性。

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.