Triterpenoids as Novel Natural Inhibitors of Human Cathepsin L

Triterpenoids as Novel Natural Inhibitors of Human Cathepsin L

Author Ramalho, Suelem D. Google Scholar
De Sousa, Lorena R. F. Google Scholar
Nebo, Liliane Google Scholar
Maganhi, Stella H. Google Scholar
Caracelli, Ignez Google Scholar
Zukerman-Schpector, Julio Google Scholar
Lima, Maria Ines S. Google Scholar
Alves, Marcio F. M. Autor UNIFESP Google Scholar
Da Silva, M. Fatima das G. F. Google Scholar
Fernandes, Joao B. Google Scholar
Vieira, Paulo C. Google Scholar
Institution Universidade Federal de São Carlos (UFSCar)
Universidade Federal de São Paulo (UNIFESP)
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 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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2010/52326-9
FAPESP: 12/22524-9
CNPq: 306121/2013-1
CNPq: 305626/2013-2
CAPES: 808/2009
Date 2014-09-01
Published in Chemistry & Biodiversity. Weinheim: Wiley-v C H Verlag Gmbh, v. 11, n. 9, p. 1354-1363, 2014.
ISSN 1612-1872 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 1354-1363
Access rights Closed access
Type Article
Web of Science ID WOS:000342625500005

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