Arylsulfonylhydrazone Induced Apoptosis in MDA-MB-... - BV FAPESP
Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Fernandes, Thais Batista [1] ; de Azevedo, Ricardo Alexandre [2] ; Yang, Rosania [1] ; Teixeira, Sarah Fernandes [2] ; Goulart Trossini, Gustavo Henrique [1] ; Marzagao Barbuto, Jose Alexandre [2] ; Ferreira, Adilson Kleber [2] ; Parise-Filho, Roberto [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, 580 Prof Lineu Prestes Av, BR-05508500 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: LETTERS IN DRUG DESIGN & DISCOVERY; v. 15, n. 12, p. 1288-1298, 2018.
Web of Science Citations: 1
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 mu M 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. (AU)

FAPESP's process: 13/19311-6 - Design, synthesis and antitumor activity of aryl-sulfonylhydrazone compounds
Grantee:Thais Batista Fernandes
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 17/00689-0 - New antineoplastic agents: synthesis, molecular docking and antitumoral activity of capsaicinoids analogues
Grantee:Roberto Parise Filho
Support Opportunities: Regular Research Grants