Antiplasmodial activity and cytotoxicity, isolation of active
alkaloids, and dereplication of Xylopia sericea leaves
ethanol extract by UPLC-DAD-ESI-MS/MS
Douglas Costa Gontijo
a
, Geraldo C elio Brand~ ao
b
, Maria Fernanda Alves do Nascimento
a
and
Alaıde Braga de Oliveira
a
a
Departamento de Produtos Farmac^euticos, Faculdade de Farmacia, Universidade Federal de Minas Gerais, Belo Horizonte and
b
Escola de
Farmacia, Universidade Federal de Ouro Preto, Ouro Preto, Brazil
Keywords
alkaloids; antiplasmodial activity;
cytotoxicity; extract dereplication;
flavonoids; UPLC-DAD-ESI-MS/MS; Xylopia
sericea
Correspondence
Alaıde Braga de Oliveira, Departamento de
Produtos Farmac^euticos, Faculdade de
Farmacia, Universidade Federal de Minas
Gerais, Av. Ant^ onio Carlos, 6627, CEP
31270-901, Belo Horizonte, MG, Brazil.
E-mail: alaidebraga@terra.com.br
Received February 23, 2018
Accepted September 17, 2018
doi: 10.1111/jphp.13029
Abstract
Objectives To assess the antiplasmodial activity of the ethanol extract of Xylopia
sericea leaves, Annonaceae, often associated with antimalarial use and to perform
a bioguided isolation of active compounds.
Methods Dereplication of ethanol extract by the UPLC-DAD-ESI-MS/MS tech-
nique allowed the identification of the major constituents, isolation and identifi-
cation of alkaloids. The antiplasmodial and cytotoxic activity of the extract,
fractions and isolated compounds was evaluated against the chloroquine-resistant
W2 strain Plasmodium falciparum and HepG2 cells, respectively.
Key findings Ethanol extract showed high reduction of parasitemia as well as
moderate cytotoxicity (86.5 3.0% growth inhibition at 50 lg/ml and CC
50
72.1 5.1 lg/ml, respectively). A total of eight flavonoids were identified, and
two aporphine alkaloids, anonaine and O-methylmoschatoline, were isolated.
Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity
(IC
50
23.2 2.7 lg/ml, CC
50
38.3 2.3 lg/ml, SI 1.6) while O-methylmoscha-
toline was not active against P. falciparum and showed a low cytotoxicity
(33.5 1.9% growth inhibition at 50 lg/ml, CC
50
274.4 0.5 lg/ml).
Conclusions Characterization of Xylopia sericea leaves ethanol extract by UPLC-
DAD-ESI-MS/MS as well as its antiplasmodial activity and the occurrence of
anonaine and O-methylmoschatoline in this Xylopia species are reported by the
first time.
Introduction
Malaria, a major global infectious disease, is endemic to 91
countries. Plasmodium falciparum is the most prevalent
malaria parasite in sub-Saharan Africa, accounting for 99%
of estimated malaria cases in 2016, and outside of Africa,
Plasmodium vivax is the predominant parasite.
[1]
In 2016,
approximately 216 million people were infected and
445 000 deaths were registered for this disease, and an esti-
mated US$ 2.7 billion was invested in malaria control and
elimination efforts globally by governments of malaria
endemic countries and international partners.
[1]
The use of
natural products for the treatment of parasitic diseases is
well-known, such as the plant species Cinchona succirubra
L. (Rubiaceae) and Artemisia annua L. (Asteraceae) in the
treatment of human malaria and fevers.
[2]
Two important
antimalarial drugs, quinine and artemisinin, were obtained
from these plants. Furthermore, chloroquine, the most
widely used antimalarial, is a synthetic quinoline struc-
turally related to quinine that was a template for its devel-
opment.
[3]
Despite the existence of an arsenal of
antimalarial drugs with significant differences in site and
mechanisms of action, control of this infection is increas-
ingly difficult due to the emergence of new Plasmodium
strains resistant to frequently used drugs.
[4]
Thus, the quest
for new antimalarial drugs is urgent once P. falciparum, the
most virulent malaria agent, also is disclosing resistance to
available drugs, including artemisinin.
Finally, plants are valuable sources of new drugs
[5]
and are
still used to treat malaria in endemic countries,
[6]
including
© 2018 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 71 (2019), pp. 260–269 260
Research Paper
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