In vitro activity of steroidal dendrimers on Trypanosoma cruzi epimastigote form with PAMAM dendrons modified by “click” chemistry |
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| Institution: | 1. Unidad de Bioquímica e Inmunología, División de Estudios de Posgrado e Investigación, Instituto Tecnológico de Oaxaca, Av. Ing. Víctor Bravo Ahuja #125 esq, Clz. Tecnológico, C.P. 68030 Oaxaca, Mexico;2. Centro de Investigación Facultad de Medicina UNAM-UABJO, Facultad de Medicina y Cirugía, Universidad Autónoma “Benito Juárez” de Oaxaca, Ex Hacienda de Aguilera S/N, Carretera a San Felipe del Agua, C.P. 68020 Oaxaca, Mexico;3. CONACyT-Instituto Politécnico Nacional, CIIDIR Unidad Oaxaca, Hornos 1003, Santa Cruz Xoxocotlán, Oaxaca C.P. 771230, Mexico;4. Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F, Apdo. Postal 14-740, 07000 Ciudad de México, Mexico;5. Facultad de Ciencias Químicas, Universidad de Colima, km 9 Carretera Colima-Coquimatlán, Colima 28400, Mexico;6. Facultad de Medicina, Departamento de Microbiología y Parasitología, UNAM, Ciudad de México 04510, Mexico;1. Department of Organic and Inorganic Chemistry, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Madrid, Spain;2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain;3. Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Gregorio Marañón (IiSGM) and Spanish BioBank VIH HGM, Madrid, Spain;1. Instituto de Estudios Avanzados (IDEA), Caracas, Venezuela;2. Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland;3. Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Caracas, Venezuela;1. Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Laboratory of Organic Synthesis, Prospect Oktyabrya 141, 450075 Ufa, Russian Federation;2. Bashkir State University, Zaki Validi Street 32, 450076 Ufa, Russian Federation;1. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China;2. Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;3. School of Pharmaceutical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;1. Instituto Tecnológico de Tepic. Av. Tecnológico #2595, Col. Lagos del Country, C. P. 63175, Tepic, Nayarit, Mexico;2. Instituto de Ciencias Básicas, Universidad Veracruzana, Dr. Luis Castelazo s/n, Col. Industrial Animas, Xalapa Ver., C.P. 91000, Mexico |
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| Abstract: | 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 IC50 = 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. |
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| Keywords: | Dendrimers Epimastigote Triazole ring |
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