Triterpenoids as Novel Natural Inhibitors of Human Cathepsin L

Autor(es):Mostrar menos -

Ramalho, Suelem D. ^[1] ; De Sousa, Lorena R. F. ^[1] ; Nebo, Liliane ^[1] ; Maganhi, Stella H. ^[2] ; Caracelli, Ignez ^[2] ; Zukerman-Schpector, Julio ^[1] ; Lima, Maria Ines S. ^[3] ; Alves, Marcio F. M. ^[4] ; Da Silva, M. Fatima das G. F. ^[1] ; Fernandes, Joao B. ^[1] ; Vieira, Paulo C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, BioMat Dept Phys, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Fed Sao Carlos, Dept Bot, BR-13565905 Sao Carlos, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Biophys, BR-04039032 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRY & BIODIVERSITY; v. 11, n. 9, p. 1354-1363, SEP 2014.
• Citações Web of Science: 3

Resumo

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 mu m 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. (AU)

• Processo FAPESP: 12/22524-9 - Síntese, caracterização e estudos de docking de sistemas de liberação controlada de fármacos e potenciais fármacos utilizando quitosana como carreador
• Beneficiário: Stella Hernandez Maganhi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/52326-9 - Estudo de produtos naturais oriundos de plantas do cerrado e mata atlântica: conhecimento químico-biológico aliado à preservação
• Beneficiário: Paulo Cézar Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular