TY - JOUR
T1 - In vitro activity of steroidal dendrimers on Trypanosoma cruzi epimastigote form with PAMAM dendrons modified by “click” chemistry
AU - Juárez-Chávez, Laura
AU - Pina-Canseco, Socorro
AU - Soto-Castro, Delia
AU - Santillan, Rosa
AU - Magaña-Vergara, Nancy E.
AU - Salazar-Schettino, Paz María
AU - Cabrera-Bravo, Margarita
AU - Pérez-Campos, Eduardo
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/5
Y1 - 2019/5
N2 - The increasing use of dendrimers shows promise for the treatment of inflammatory diseases, Chagas disease and other conditions such as cancer. In this study, the activity of 1st and 2nd generation dendrimers over T. cruzi in the epimastigote stage was tested. Dendrimers were derived from α-ethynylestradiol (EE) modified with PAMAM-type dendrons through a triazole ring. The activity of each compound was evaluated in five doses (from 1.3 to 20 µmol/mL) by flow cytometry, including benznidazole (Bz) as positive control. The findings show that an equivalent concentration of 14.8 µmol/mL of 2nd generation (G) dendrimer is 8 times more effective than Bz at 24 h, and it maintains its superiority at 48 h with an IC 50 = 1.25 ± 0.19 µmol/mL. A TUNEL assay showed that dendrimers induce cell death in T. cruzi epimastigotes mostly via apoptosis, unlike Bz, which induces death via necrosis in more than 50% of cells.
AB - The increasing use of dendrimers shows promise for the treatment of inflammatory diseases, Chagas disease and other conditions such as cancer. In this study, the activity of 1st and 2nd generation dendrimers over T. cruzi in the epimastigote stage was tested. Dendrimers were derived from α-ethynylestradiol (EE) modified with PAMAM-type dendrons through a triazole ring. The activity of each compound was evaluated in five doses (from 1.3 to 20 µmol/mL) by flow cytometry, including benznidazole (Bz) as positive control. The findings show that an equivalent concentration of 14.8 µmol/mL of 2nd generation (G) dendrimer is 8 times more effective than Bz at 24 h, and it maintains its superiority at 48 h with an IC 50 = 1.25 ± 0.19 µmol/mL. A TUNEL assay showed that dendrimers induce cell death in T. cruzi epimastigotes mostly via apoptosis, unlike Bz, which induces death via necrosis in more than 50% of cells.
KW - Dendrimers
KW - Epimastigote
KW - T. cruzi
KW - Triazole ring
UR - http://www.scopus.com/inward/record.url?scp=85061435456&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2019.01.056
DO - 10.1016/j.bioorg.2019.01.056
M3 - Artículo
C2 - 30772646
SN - 0045-2068
VL - 86
SP - 452
EP - 458
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -