RT info:eu-repo/semantics/article
T1 Flavonoids from Piper Species as Promising Antiprotozoal Agents against Giardia intestinalis: Structure-Activity Relationship and Drug-Likeness Studies
A1 Ticona, Juan C.
A1 Bilbao Ramos, Pablo
A1 Amesty, Ángel
A1 Flores, Ninoska
A1 Dea Ayuela, M. Auxiliadora
A1 López Bazzocchi, Isabel
A1 Jiménez Díaz, Ignacio Antonio
K1 Piper species
K1 flavonoids
K1 Giardia intestinalis
K1 structure-activity relationship
K1 drug-likeness
AB Diarrhea diseases caused by the intestinal protozoan parasite Giardia intestinalis are amajor global health burden. Moreover, there is an ongoing need for novel anti-Giardia drugs due todrawbacks with currently available treatments. This paper reports on the isolation and structuralelucidation of six new flavonoids (1–6), along with twenty-three known ones (7–29) from the Piperspecies. Their structures were established by spectroscopic and spectrometric techniques. Flavonoidswere tested for in vitro antiprotozoal activity against Giardia intestinalis trophozoites. In addition,structure-activity relationship (SAR) and in silico ADME studies were performed to understandthe pharmacophore and pharmacokinetic properties of these natural compounds. Eight flavonoidsfrom this series exhibited remarkable activity in the micromolar range. Moreover, compound 4 wasidentified as having a 40-fold greater antiparasitic effect (IC50 61.0 nM) than the clinical reference drug,metronidazole (IC50 2.5 µM). This antiprotozoal potency was coupled with an excellent selectivityindex (SI 233) on murine macrophages and in silico drug-likeness. SAR studies revealed that thesubstitution patterns, type of functional group, and flavonoid skeleton played an essential role in theactivity. These findings highlight flavonoid 4 as a promising candidate to develop new drugs for thetreatment of Giardia infections.
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/35926
UL http://riull.ull.es/xmlui/handle/915/35926
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 19-nov-2024