A SEMI-SYNTHETIC MOLECULE DERIVED FROM DEHYDROLEUCODINE AFFECTS THE TRYPANOSOMA CRUZI CELL CYCLE

GOMEZ J; GUARISE C; CIFUENTES D; MIGUEL A. SOSA; BARRERA P

Congreso; XXXVII Reunión Anual de la Sociedad de Biología de Cuyo; 2019

Sociedad de Biología de Cuyo

Trypanosoma cruzi is a parasite causing Chagas disease, which is endemic in Latin America, but in the last 20 years, it has expandedworldwide. The current treatment is restricted to Nifurtimox and Benznidazole, but both are relatively toxic and have limited efficacyon the patients. The development of new effective therapeutic agents is urgently needed. The sesquiterpene lactones (STLs) arenatural compounds purified from native plants of Argentina with multiple pharmacological applications. The STL dehydroleucodine(DhL), has an alpha-methylene group that could react with multiple sulfhydryl group-containing proteins, affecting cellular functionssuch as proliferation, the activity mitochondrial, leading to the cell death/apoptosis. This study is focused on elucidating the actionmechanisms of DhL and its derivative DC-X11, obtained by chemical substitution, on T. cruzi epimastigotes (strain Dm28c). Weobserved that DhL and DC-X11 have antiproliferative and cytostatic effects on the parasites. By morphological and ultrastructuralstudies, we observed an increase of parasites with multiple cell nuclei, kinetoplasts, or flagella after the treatment with DC-X11,suggesting an effect on late steps of the cell cycle (i.e., cellular division). These results were confirmed with parasites synchronizedwith hydroxyurea (HU 20 mM) for 24 h, and then they were treated with the compound. We concluded that the derivative DC-X11inhibits T. cruzi proliferation by delaying the progression of the cell division. Further studies are necessary to identify the moleculartargets affected by DC-X11.