Triterpenoids as Novel Natural Inhibitors of Human Cathepsin L |
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| Authors: | Suelem D Ramalho Lorena R F De?Sousa Liliane Nebo Stella H Maganhi Ignez Caracelli Julio Zukerman‐Schpector Maria Inês S Lima Marcio F M Alves M Fátima das G F Da?Silva João B Fernandes Paulo C Vieira |
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| Institution: | 1. Department of Chemistry, Federal University of S?o Carlos, 13565‐905 S?o Carlos, SP, Brazil, (phone: +55‐16‐33518061;2. fax: +55‐16‐33518350);3. BioMat‐Department of Physics, Federal University of S?o Carlos, 13565‐905 S?o Carlos, SP, Brazil;4. Department of Botany, Federal University of S?o Carlos, 13565‐905 S?o Carlos, SP, Brazil;5. Department of Biophysics, Federal University of S?o Paulo, 04039?–?032 S?o Paulo, SP, Brazil |
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| Abstract: | 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. |
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| Keywords: | Triterpenoids Cathepsin L Inhibitors |
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