Synthesis, Molecular Docking and Biological Activity Evaluation of Alkoxy Substituted Chalcone Derivatives: Potential Apoptosis Inducing Agent on MCF-7 Cells

Author(s): Wan M. Khairul*, Fatimah Hashim*, Mas Mohammed, Nurul S.M.N. Shah, Syed A.T.T. Johari, Rafizah Rahamathullah, Adibah I. Daud, Nyuk L. Ma

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 21 , Issue 13 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Introduction: In this contribution, a series of alkoxy substituted chalcones were successfully designed, synthesized, spectroscopically characterized and evaluated for their cytotoxicity potential in inhibiting the growth of MCF-7 cells.

Objective: In order to investigate the influence between electron density in conjugated π-systems and biological activities, different withdrawing substituents, namely Nitro (NO2), Cyano (C≡N) and trifluoromethyl (CF3) were introduced in the chalcone-based molecular system.

Methods: All the derivatives were then tested on MCF-7 cell line using the fluorescence microscopy-based cytotoxicity analyses.

Results: The preliminary findings showed that both –NO2 and –CF3 substituents revealed their potential to inhibit the growth of MCF-7 with IC50 values of 14.75 and 13.75 μg/ml, respectively. In addition, the morphological changes of MCF-7 cells were observed in response to alkoxy substituted chalcone treatment through an induction of apoptosis pathway with cell blebbing, phosphatidylserine exposure and autophagic activity with acidification of lysosomal structure. Intermolecular interaction based on in silico investigation on nitro, trifluoromethyl and cyano based chalcones exhibited several types of interactions with tumor necrosis factor receptor (PDB: 1EXT) protein and high hydrogen bond in the molecule-receptor interaction have given significant impact towards their toxicity on MCF-7 cells.

Conclusion: Significantly, these types of chalcones exhibited ideal and high potential to be further developed as anti-cancer agents.

Keywords: Chalcone, spectroscopy, MCF-7 cells, apoptosis, autophagy, TNFR.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 10 November, 2020
Page: [1738 - 1750]
Pages: 13
DOI: 10.2174/1871520620999201110190709
Price: $65

Article Metrics

PDF: 250