Chalcone Derivative Induces Flagellar Disruption and Autophagic Phenotype in Phytomonas serpens In Vitro.

Phytomonas serpens is a trypanosomatid phytoparasite, found in a great variety of species, including tomato plants. It is a significant problem for agriculture, causing high economic loss. In order to reduce the vegetal infections, different strategies have been used. The biological activity of molecules obtained from natural sources has been widely investigated to treat trypanosomatids infections. Among these compounds, chalcones have been shown to have anti-parasitic and anti-inflammatory effects, being described as having a remarkable activity on trypanosomatids, especially in Leishmania species. Here, we evaluated the antiprotozoal activity of the chalcone derivative (NaF) on P. serpens promastigotes, while also assessing its mechanism of action. The results showed that treatment with the derivative NaF for 24 h promotes an important reduction in the parasite proliferation (IC50/24 h = 23.6 ± 4.6 µM). At IC50/24 h concentration, the compound induced an increase in reactive oxygen species (ROS) production and a shortening of the unique flagellum of the parasites. Electron microscopy evaluation reinforced the flagellar phenotype in treated promastigotes, and a dilated flagellar pocket was frequently observed. The treatment also promoted a prominent autophagic phenotype. An increased number of autophagosomes were detected, presenting different levels of cargo degradation, endoplasmic reticulum profiles surrounding different cellular structures, and the presence of concentric membranar structures inside the mitochondrion. Chalcone derivatives may present an opportunity to develop a treatment for the P. serpens infection, as they are easy to synthesize and are low in cost. In order to develop a new product, further studies are still necessary.

Synthesis of chalcone derivatives by Claisen-Schmidt condensation and in vitro analyses of their antiprotozoal activities.

Chalcone is a molecule with known biological activities. Based on this, a series of chalcone derivatives bearing methyl, phenyl or furanyl substituents at different positions of A and B rings were synthesised, characterised, and evaluated regarding antiprotozoal activity. Molecules were synthesised via base catalyzed Claisen-Schmidt condensation and characterised by IR and NMR spectral data. Antiprotozoal activity against Phytomonas serpens, Leishmania amazonensis and Acanthamoeba polyphaga was performed. All compounds inhibited more than 50% of the growth of P. serpens while five had this effect on L. amazonensis and all of them no more than 35% of inhibition on A. polyphaga. Remarkably interesting antiprotozoal effects were recorded with compound 5, with IC50 of 1.59 µM for P. serpens and 11.49 µM for L. amazonensis. The addition of a naphthyl group to the B ring can be postulated to be the cause of the 10 times increase observed in its trypanocidal activity.