N,N′-双取代脲类克鲁斯氏锥体虫半胱氨酸蛋白酶小分子抑制剂的合成及其活性研究

Synthesis and Bioactivity of N,N′-Bis-substitute d Urea Derivatives as Novel Small Molecular Inhibitors of Cysteine Protease of Tryp anosoma cruzi

目的 :寻找克鲁斯氏锥体虫体半胱氨酸蛋白酶 (Cruzain)的小分子抑制剂。方法 :根据对Cruzain分子结构的计算机模拟设计结果 ,选用N ,N′ 双取代脲为先导结构 ,设计并合成了 2 1个未见文献报道的双取代脲衍生物 ,确证了它们的化学结构 ,测定了化合物的体外抑制Cruzain的IC50 值。结果 :生物活性测定结果显示所合成的化合物均有不同程度的抑制Cruzain的活性 ,其中化合物Ⅳ8、Ⅳ9和Ⅳ1 7的活性与对照药tf

AIM:To search for the small molecular inh ibitors of cysteine protease of Trypanosoma Cruzi. METHOD: Th e N,N′-bis-substituted urea was chosen as the lead scaffold based on the comp utational molecular modeling of cruzain. Total 21 new compounds that had never b een reported were designed and synthesized . The structures of synthesized comp o unds were confirmed by 1 HNMR spectroscopy and HRMS(EI). The bioass ay of the co mpounds against cruzain in vitro has also been done. RESULT: All synthesized compounds exhibited certain activities against crizain in vitro,in which the IC 50 value of compound Ⅳ 8 ,Ⅳ 9 and Ⅳ 17 was as same as that of tf-175