Ramalho Suelem D, De Sousa Lorena R F, Nebo Liliane, Maganhi Stella H, Caracelli Ignez, Zukerman-Schpector Julio, Lima Maria Inês S, Alves Marcio F M, Da Silva M Fátima das G F, Fernandes João B, Vieira Paulo C
Department of Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP, Brazil, (phone: +55-16-33518061; fax: +55-16-33518350).
Chem Biodivers. 2014 Sep;11(9):1354-63. doi: 10.1002/cbdv.201400065.
Cathepsins L (catL) and B play an important role in tumor progression and have been considered promising therapeutic targets in the development of novel anticancer agents. Using a bioactivity-guided fractionation, a series of triterpenoids was identified as a new class of competitive inhibitors towards cathepsin L with affinity values in micromolar range. Among the 14 compounds evaluated, the most promising were 3-epiursolic acid (3), 3-(hydroxyimino)oleanolic acid (9), and 3-(hydroxyimino)masticadienoic acid (13) with IC50 values of 6.5, 2.4, and 2.6 μM on catL, respectively. Most of the evaluated triterpenoids do not inhibit cathepsin B. Thus, the evaluated compounds exhibit a great potential to help in the design of new inhibitors with enhanced potency and affinity towards catL. Docking studies were performed in order to gain insight on the binding mode and SAR of these compounds.
组织蛋白酶L（catL）和B在肿瘤进展中起重要作用，并且在新型抗癌药物的开发中被认为是有前景的治疗靶点。通过生物活性导向的分级分离，一系列三萜类化合物被鉴定为对组织蛋白酶L的一类新型竞争性抑制剂，其亲和力值在微摩尔范围内。在评估的14种化合物中，最有前景的是3-表乌苏酸（3）、3-（羟基亚氨基）齐墩果酸（9）和3-（羟基亚氨基）乳香二烯酸（13），它们对catL的IC50值分别为6.5、2.4和2.6 μM。大多数评估的三萜类化合物不抑制组织蛋白酶B。因此，评估的化合物在设计对catL具有增强效力和亲和力的新抑制剂方面具有巨大潜力。进行对接研究以深入了解这些化合物的结合模式和构效关系。
