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Design, Synthesis and Biological Evaluation of 1H-1,2,3-Triazole-Linked-1H-Dibenzo[b,h]xanthenes as Inductors of ROS-Mediated Apoptosis in the Breast Cancer Cell Line MCF-7

[ Vol. 15 , Issue. 2 ]

Author(s):

Carolina S. Bortolot, Luana da S.M. Forezi, Roberta K.F. Marra, Marcelo I.P. Reis, Bárbara V.F.e Sá, Ricardo I. Filho, Zeinab Ghasemishahrestani, Mauro Sola-Penna, Patricia Zancan, Vitor F. Ferreira* and Fernando de C. da Silva*   Pages 119 - 129 ( 11 )

Abstract:


Background: Low molecular weight 1,2,3-triazoles and naphthoquinones are endowed with various types of biological activity, such as against cancer, HIV and bacteria. However, in some cases, the conjugation of these two nuclei considerably increases their biological activities.

Objective: In this work, we decided to study the synthesis and screening of bis-naphthoquinones and xanthenes tethered to 1,2,3-triazoles against cancer cell lines, specifically the human breast cancer cell line MCF-7.

Results: Starting from lawsone and aryl-1H-1,2,3-triazole-4-carbaldehydes (10a-h) several new 7- (1-aryl-1H-1,2,3-triazol-4-yl)-6H-dibenzo[b,h]xanthene-5,6,8,13(7H)-tetraones (12a-h) and 3,3'- ((1-aryl-1H-1,2,3-triazol-4-yl)methylene)bis(2-hydroxynaphthalene-1,4-diones) 11a-h were synthesized and evaluated for their cytotoxic activities using the human breast cancer cell line MCF-7 and the non-tumor cell line MCF10A as control. We performed test of cell viability, cell proliferation, intracellular ATP content and cell cytometry to determine reactive oxygen species (ROS) formation.

Conclusions: Based on these results, we found that compound 12a promotes ROS production, interfering with energy metabolism, cell viability and proliferation, and thus promoting whole cell damage.

Keywords:

Cell viability, naphthoquinones, lawsone, MTT assay, ATP, CyQuant assay.

Affiliation:

Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, CEP 24020-150, Niteroi-RJ, Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, CEP 24020-150, Niteroi-RJ, Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, CEP 24020-150, Niteroi-RJ, Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, CEP 24020-150, Niteroi-RJ, Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, CEP 24020-150, Niteroi-RJ, Universidade Federal do Rio de Janeiro, Laboratorio de Oncobiologia Molecular (LabOMol), Departamento de Biotecnologia Farmaceutica, Faculdade de Farmacia, CEP 21941-902, Rio de Janeiro-RJ, Universidade Federal do Rio de Janeiro, Laboratorio de Oncobiologia Molecular (LabOMol), Departamento de Biotecnologia Farmaceutica, Faculdade de Farmacia, CEP 21941-902, Rio de Janeiro-RJ, Universidade Federal do Rio de Janeiro, Laboratorio de Enzimologia e Controle do Metabolismo (LabECoM) Departamento de Biotecnologia Farmaceutica, Faculdade de Farmacia, CEP 21941-902, Rio de Janeiro-RJ, Universidade Federal do Rio de Janeiro, Laboratorio de Oncobiologia Molecular (LabOMol), Departamento de Biotecnologia Farmaceutica, Faculdade de Farmacia, CEP 21941-902, Rio de Janeiro-RJ, Universidade Federal Fluminense, Departamento de Tecnologia Farmaceutica, Faculdade de Farmacia, R. Dr. Mario Vianna, 523, Santa Rosa, CEP 24241-002, Niteroi-RJ, Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, CEP 24020-150, Niteroi-RJ

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