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Secochiliolide ester derivatives: Preparation and evaluation of their antitrypanosomal and antimalarial efficacy
Author(s) -
Ronchi Romina J.,
Beaufay Claire,
Bero Joanne,
Robirosa Juan B.,
Mazzuca Marcia,
Palermo Jorge A.,
QuetinLeclercq Joëlle,
Sánchez Marianela
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13392
Subject(s) - trypanosoma brucei , antiparasitic , plasmodium falciparum , pharmacology , in vivo , cytotoxicity , selectivity , diterpene , chemistry , in vitro , stereochemistry , biology , malaria , biochemistry , medicine , immunology , microbiology and biotechnology , pathology , gene , catalysis
In the present study, a series of new esters of secochiliolide acid ( SA ), a diterpene isolated from Nardophyllum bryoides, were synthesized in good yield. All compounds were evaluated for their in vitro antiparasitic properties (on Plasmodium falciparum and Trypanosoma brucei brucei ) and cytotoxicity (on WI 38, normal mammalian cells). They displayed moderate antitrypanosomal activity with IC 50 values between 2.55 and 18.14 μ m , with selectivity indices >10, and low antiplasmodial effects with IC 50 > 29 μ m . The only exception was the n ‐hexyl ester of SA , which showed a strong and selective antiplasmodial activity ( IC 50 = 1.99 μ m and selectivity index = 117.0). The in vivo antimalarial efficacy of this compound was then assessed according to the 4‐day suppressive test of Peters in mice. An intraperitoneal treatment at 50 mg kg −1 day −1 induced a slight parasitaemia reduction by 56% which was statistically significant on day 4 post‐infection and an increase in the survival time.