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BACKGROUND   Kaempferol (KPF) is a flavonoid with antiparasitic activity including experimental giardiasis which mechanism of action is unknown.    OBJECTIVE   To analyse the cytotoxic effects of KPF on  Giardia duodenalis  trophozoites and to identify a likely parasite target of this compound.    METHODS   We used inhibitory concentrations of KPF (IC 25 , IC 50  and IC 100 ) and albendazole (ABZ) as reference drug. The ultrastructure of the trophozoites was analysed by transmission electron microscopy (TEM) whilst apoptosis/necrosis, production of reactive oxygen species (ROS) and cell cycle progression were assessed by flow cytometry (FCM) and confocal laser microscopy (CLM). Ligand-protein docking analyses were carried out using KPF structure from a drug library and crystal structure of a  G. duodenalis  aldose reductase ( GdAldRed ) homolog.    RESULTS   KPF provoked appearance of perinuclear and periplasmic spaces devoid of cytosolic content and multilamellar structures. KPF induced proapoptotic death associated with partial arrest in the S phase without ROS production. Bioinformatics approaches predicted that  GdAldRed  is a viable KPF target (ΔG = -7.09 kCal/mol), exhibiting 92% structural identity and a similar coupling pattern as its human homolog.    CONCLUSIONS   KPF exerted a proapoptotic effect on  G. duodenalis  trophozoites involving partial interruption of DNA synthesis without oxidative stress or structure damage to chromatin and cytoskeletal structures.  GdAldRed  is a likely target underlying its antigiardial activity.

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Ultrastructural and proapoptotic-like effects of kaempferol in Giardia duodenalis trophozoites and bioinformatics prediction of its potential protein target