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Improvement of the Anticancer Activity of Chlorambucil and Ibuprofen via Calix[4]arene Conjugates

Author(s):

Luis D. Pedro-Hernández, Ulises Organista-Mateos, Luis Isaac Allende-Alarcón, Elena Martínez-Klimova*, Teresa Ramírez-Ápan and Marcos Martínez-García  

Abstract:


Background: One of the possible ways of improving the activity and selectivity profile of anticancer agents is to design drug carrier systems employing nanomolecules. Calix[4]arene derivatives and chlorambucil and ibuprofen are important compounds that exhibit interesting anticancer properties.

Objective: The objective of this article is the synthesis of new calix[4]arene-derivative conjugates of chlorambucil or ibuprofen with potential anticancer activity.

Methods: Cytotoxicity assays were determined using the protein-binding dye sulforhodamine B (SRB) in microculture to measure cell growth, as described [19,20]. Conjugates of chlorambucil and resorcinarene-dendrimers were prepared in 2% DMSO and added into the culture medium immediately before use. Control cells were treated with 2% DMSO.

Results: Thus, calix[4]arene-derivative conjugates of chlorambucil or ibuprofen showed good stability of the chemical link between drug and spacer. Evaluation of the cytotoxicity of the calix[4]arene chlorambucil or ibuprofen conjugates employing a sulforhodamine B (SRB) assay in K-562 (human chronic myelogenous leukemia cells) and U-251 (human glioblastoma cells) demonstrated that the conjugate was more potent as an antiproliferative agent than free chlorambucil and ibuprofen. The conjugates did not show any activity against the COS-7 African green monkey kidney fibroblast cell line.

Conclusion: In the paper we report the synthesis and spectroscopic analyses of new calix[4]arene derivative conjugates of chlorambucil or ibuprofen. Cytotoxicity assays revealed that at 10 μM, the conjugates were very active against K-562 (human chronic myelogenous leukemia cells) and U-251 (human glioblastoma cells) cancer cells' proliferation. In order to explain the molecular mechanisms involved in anticancer activity of calix[4]arene chlorambucil or ibuprofen conjugates, our research will be continued.

Keywords:

chlorambucil, ibuprofen, calix[4]arene derivatives, anticancer activity

Affiliation:

Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C.P. 04510, México D.F., Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C.P. 04510, México D.F., Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C.P. 04510, México D.F., Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Interior, Coyoacán, C.P. 04510, México D.F., Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C.P. 04510, México D.F., Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Coyoacán, C.P. 04510, México D.F.



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