RT info:eu-repo/semantics/article
T1 Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB
A1 Pérez Pertejo, Maria Yolanda
A1 Escudero Martínez, José Miguel
A1 Reguera Torres, Rosa María
A1 Balaña Fouce, Rafael
A1 García, Pablo A.
A1 Jambrina, Pablo G.
A1 San Feliciano Martín, Arturo
A2 Toxicologia
K1 Farmacología
K1 Medicina. Salud
K1 Leishmania infantum
K1 Terpenylquinones
K1 Naphthoquinones
K1 Anthraquinones
K1 Acridinequinone
K1 DNA-Topoisomerase IB
K1 3109 Ciencias Veterinarias
K1 3214 Toxicología
AB [EN] Leishmania is the aethiological agent responsible for the visceral leishmaniasis, a serious parasite-borne disease widely spread all over the World. The emergence of resistant strains makes classical treatments less effective; therefore, new and better drugs are necessary. Naphthoquinones are interesting compounds for which many pharmacological properties have been described, including leishmanicidal activity. This work shows the antileishmanial effect of two series of terpenyl-1,4-naphthoquinones (NQ) and 1,4-anthraquinones (AQ) obtained from natural terpenoids, such as myrcene and myrceocommunic acid. They were evaluated both in vitro and ex vivo against the transgenic iRFP-Leishmania infantum strain and also tested on liver HepG2 cells to determine their selectivity indexes. The results indicated that NQ derivatives showed better antileishmanial activity than AQ analogues, and among them, compounds with a diacetylated hydroquinone moiety provided better results than their corresponding quinones. Regarding the terpenic precursor, compounds obtained from the monoterpenoid myrcene displayed good antiparasitic efficiency and low cytotoxicity for mammalian cells, whereas those derived from the diterpenoid showed better antileishmanial activity without selectivity. In order to explore their mechanism of action, all the compounds have been tested as potential inhibitors of Leishmania type IB DNA topoisomerases, but only some compounds that displayed the quinone ring were able to inhibit the recombinant enzyme in vitro. This fact together with the docking studies performed on LTopIB suggested the existence of another mechanism of action, alternative or complementary to LTopIB inhibition. In silico druglikeness and ADME evaluation of the best leishmanicidal compounds has shown good predictable druggability
PB Elsevier
SN 2211-3207
LK https://hdl.handle.net/10612/17813
UL https://hdl.handle.net/10612/17813
NO Pérez-Pertejo, Y., Escudero-Martínez, J. M., Reguera, R. M., Balaña-Fouce, R., García, P. A., Jambrina, P. G., San Feliciano, A., & Castro, M.-Á. (2019). Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB. International Journal for Parasitology: Drugs and Drug Resistance, 11, 70-79. https://doi.org/10.1016/J.IJPDDR.2019.10.004
DS BULERIA. Repositorio Institucional de la Universidad de León
RD Jul 6, 2024