@misc{10481/98877,
year = {2020},
month = {11},
url = {https://hdl.handle.net/10481/98877},
abstract = {The life-long and life-threatening Chagas disease is
one of the most neglected tropical diseases caused by the
protozoan parasite Trypanosoma cruzi. It is a major public health
problem in Latin America, as six to seven million people are
infected, being the principal cause of mortality in many endemic
regions. Moreover, Chagas disease has become widespread due to
migrant populations. Additionally, there are no vaccines nor
effective treatments to fight the disease because of its long-term
nature and complex pathology. Therefore, these facts emphasize
how crucial the international effort for the development of new
treatments against Chagas disease is. Here, we present the in vitro
and in vivo trypanocidal activity of some oxygenated abietane diterpenoids and related compounds. The 1,4-benzoquinone 15, not
yet reported, was identified as a fast-acting trypanocidal drug with efficacy against different strains in vitro and higher activity and
lower toxicity than benznidazole in both phases of murine Chagas disease. The mode of action was also evaluated, suggesting that
quinone 15 kills T. cruzi by inducing mitochondrion-dependent necrosis through a bioenergetics collapse caused by a mitochondrial
membrane depolarization and iron-containing superoxide dismutase inhibition. Therefore, the abietane 1,4-benzoquinone 15 can be
considered as a new candidate molecule for the development of an appropriate and commercially accessible anti-Chagas drug.},
organization = {Spanish Ministry of
Economy and Competitiveness (CSD2010-00065 and
CTQ2014-56611-R/BQU)},
organization = {European
Regional Development Fundings (ERDF)},
organization = {FPU Grant (FPU14/01537) from the Ministry
of Education of Spain},
title = {In vivo biological evaluation of a synthetic royleanone derivative as a promising fast-acting trypanocidal agent by inducing mitochondrial-dependent necrosis},
doi = {https://dx.doi.org/10.1021/acs.jnatprod.0c00651},
author = {Martín Escolano, Rubén and Guardia Monteagudo, Juan José and Martín Escolano, Javier and Cirauqui, Nuria and Fernández Vargas, Antonio Jesús and Rosales Lombardo, María José and Chahboun Karimi, Rachid and Sánchez Moreno, Manuel and Álvarez De Manzaneda Roldán, Enrique and Marín Sánchez, Clotilde},
}