Triterpenoids as novel natural inhibitors of human cathepsin L
| Autor: | Maria Inês Salgueiro Lima, Ignez Caracelli, Suelem D. Ramalho, Stella H. Maganhi, M. Fátima das G. F. da Silva, João B. Fernandes, Paulo C. Vieira, Liliane Nebo, Lorena R.F. de Sousa, Marcio F.M. Alves, Julio Zukerman-Schpector |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Cathepsin L Myrtaceae Drug Evaluation Preclinical Bioengineering Cysteine Proteinase Inhibitors Biochemistry chemistry.chemical_compound Triterpenoid Ic50 values Potency Humans Molecular Biology Oleanolic acid Cathepsin biology General Chemistry General Medicine Triterpenes Molecular Docking Simulation chemistry Docking (molecular) Tumor progression biology.protein Molecular Medicine |
| Zdroj: | Chemistrybiodiversity. 11(9) |
| ISSN: | 1612-1880 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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