Title:Improvement of the Anticancer Activity of Chlorambucil and Ibuprofen via Calix[4]arene Conjugates
Volume: 16
Issue: 7
Author(s): Luis D. Pedro-Hernández, Ulises Organista-Mateos, Luis I. Allende-Alarcón, Elena Martínez-Klimova*, Teresa Ramírez-Ápan and Marcos Martínez-García
Affiliation:
- Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Circuito Interior, Coyoacan, C.P. 04510, Mexico D.F.,Mexico
Keywords:
Chlorambucil, calixarenes, ibuprofen, calix[4]arene derivatives, anticancer activity, human glioblastoma cells.
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 the anticancer activity of calix[4]arene chlorambucil or ibuprofen conjugates,
our research will be continued.