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Triterpenoids as Novel Natural Inhibitors of Human Cathepsin L
Author(s) -
Ramalho Suelem D.,
De Sousa Lorena R. F.,
Nebo Liliane,
Maganhi Stella H.,
Caracelli Ignez,
ZukermanSchpector Julio,
Lima Maria Inês S.,
Alves Marcio F. M.,
Da Silva M. Fátima das G. F.,
Fernandes João B.,
Vieira Paulo C.
Publication year - 2014
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201400065
Subject(s) - oleanolic acid , chemistry , triterpenoid , cathepsin , cathepsin l , biochemistry , potency , enzyme , stereochemistry , pharmacology , in vitro , biology , medicine , alternative medicine , pathology
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 IC 50 values of 6.5, 2.4, and 2.6 μ 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.