TY - JOUR
T1 - Virtual screening of fda‐approved drugs against triose phosphate isomerase from entamoeba histolytica and giardia lamblia identifies inhibitors of their trophozoite growth phase
AU - Juárez‐saldivar, Alfredo
AU - Barbosa‐cabrera, Elizabeth
AU - Lara‐ramírez, Edgar E.
AU - Paz‐gonzález, Alma D.
AU - Martínez‐vázquez, Ana V.
AU - Bocanegra‐garcía, Virgilio
AU - Palos, Isidro
AU - Campillo, Nuria E.
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histo-lytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure‐based virtual screening of FDA‐approved drugs was per-formed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05‐4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).
AB - Infectious diseases caused by intestinal protozoan, such as Entamoeba histolytica (E. histo-lytica) and Giardia lamblia (G. lamblia) are a worldwide public health issue. They affect more than 70 million people every year. They colonize intestines causing primarily diarrhea; nevertheless, these infections can lead to more serious complications. The treatment of choice, metronidazole, is in doubt due to adverse effects and resistance. Therefore, there is a need for new compounds against these parasites. In this work, a structure‐based virtual screening of FDA‐approved drugs was per-formed to identify compounds with antiprotozoal activity. The glycolytic enzyme triosephosphate isomerase, present in both E. histolytica and G. lamblia, was used as the drug target. The compounds with the best average docking score on both structures were selected for the in vitro evaluation. Three compounds, chlorhexidine, tolcapone, and imatinib, were capable of inhibit growth on G. lamblia trophozoites (0.05‐4.935 μg/mL), while folic acid showed activity against E. histolytica (0.186 μg/mL) and G. lamblia (5.342 μg/mL).
KW - Drug repositioning
KW - FDA
KW - Molecular docking
KW - Protozoa
KW - Virtual screening
UR - http://www.scopus.com/inward/record.url?scp=85106904704&partnerID=8YFLogxK
U2 - 10.3390/ijms22115943
DO - 10.3390/ijms22115943
M3 - Artículo
C2 - 34073021
AN - SCOPUS:85106904704
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 11
M1 - 5943
ER -