Arylsulfonylhydrazone Induced Apoptosis in MDA-MB-231 Breast Cancer Cells

Author(s): Thais Batista Fernandes, Ricardo Alexandre de Azevedo, Rosania Yang, Sarah Fernandes Teixeira, Gustavo Henrique Goulart Trossini, Jose Alexandre Marzagao Barbuto, Adilson Kleber Ferreira, Roberto Parise-Filho*

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 12 , 2018

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Graphical Abstract:


Background: Breast cancer is the most frequent cancer among women. Chemotherapy is necessary for treating metastatic disease and represents an important therapeutic approach, although antineoplastic drugs have high toxicity and may be limited by the development of drug resistance. These problems impose an urgent need to discover new anticancer agents and, so, arylsulfonylhydrazone analogues were designed, synthesized, and evaluated with regard to their cytotoxic activity against breast cancer cells in order to identify novel potential antitumor agents.

Methods: Synthesis was performed as previously described by Fernandes and co-workers. Cytotoxicity of sulfonylhydrazones against MDA-MB-231, MCF-7 and 3T3 cells was evaluated by MTT method. Apoptotic effects was verified by Annexin-V/PI assay, Hoechst stain and propidium iodide stain. Molecular modeling was executed using Spartan’10 version 1.1.0. Geometry optimization was performed by the MMFF, PM6 and Hartree-Fock 3-31G* methods and electronic and lipophilic properties were computed.

Results: Thirteen analogues were synthesized, which 3f and 4f were cytotoxic against evaluated breast cancer cells. The most promising compound, 3f, showed IC50 values equal to 104.6 and 142.4 µM for MDA-MB-231 and MCF-7, respectively. 3f induced apoptosis, causing phosphatidylserine externalization, pyknosis, and cell cycle arrest in the G0/G1 phase in MDA-MB-231 breast cancer cells. Furthermore, 3f was selective for tumor cells when compared to 3T3 fibroblasts. Structure- activity relationship suggests that introduction of a benzodioxol group increased cytotoxicity and superior lipophilicity may be related to superior activity.

Conclusion: Sulfonylhydrazone analogues presented good activity against breast cancer cells by inducing apoptosis and might be a promising scaffold to further molecular modifications persuing more effective antitumoral agents.

Keywords: Breast cancer, antitumor agents, arylsulfonylhydrazone, cytotoxicity, molecular modification, drug design.

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Article Details

Year: 2018
Published on: 16 October, 2018
Page: [1288 - 1298]
Pages: 11
DOI: 10.2174/1570180815666180321161513
Price: $65

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