Novel selenylated imidazo[1,2-a]pyridines for breast cancer chemotherapy: Inhibition of cell proliferation by Akt-mediated regulation, DNA cleavage and apoptosis.

Abstract

A novel series of selenylated imidazo[1,2-a]pyridines were designed and synthesized with a view to a promising activity against breast cancer cell. The compounds, 7-methyl-3-(naphthalene-1-ylselanyl)-2-phenylimidazo[1,2-a]pyridine, named IP-Se-05, and 3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazo[1,2-a]pyridine, named IP-Se-06, showed high cytotoxicity for MCF-7 cells (IC50 = 26.0 μM and 12.5 μM, respectively). Both the compounds inhibited the cell proliferation and caused decrease in the number of cells in the G2/M phase of cell cycle. IP-Se-05 and IP-Se-06 were also evaluated for effects on CT-DNA and DNA of MCF-7 cells. The compounds intercalated into CT-DNA and both treatments caused cleavage of DNA in cells. In addition, the compounds induced cell death by apoptosis. However, the presence of (2-methoxyphenyl) selenyl moiety at the imidazo[1,2-a]pyridine (IP-Se-06) appears to have a better antitumor effect with higher cytotoxicity at a lower concentration and caused less necrosis. Overall, the current study established IP-Se-06 more than IP-Se-05 as a potential prototype compound to be employed as an antiproliferative agent for the treatment of breast cancer.

• Authors: Gabriela M Almeida, Jamal Rafique, Sumbal Saba, Tâmila Siminski, Nádia S R S Mota, Danilo Wilhelm Filho, Antonio Luiz Braga, Rozangela Curi Pedrosa, Fabiana Ourique
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 503 Issue 3 Pg. 1291-1297 (09 10 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 30017191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Pyrimidines
• imidazo(1,2-a)pyrimidine
• Proto-Oncogene Proteins c-akt

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Cycle Checkpoints (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• DNA Cleavage (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Humans
• Molecular Structure
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyrimidines (chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured