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

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

Volume: 21 Issue: 13

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

Affiliation:

• Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu,Malaysia

• Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu,Malaysia

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

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.

Cite this article as:

Khairul M. Wan *, Hashim Fatimah *, Mohammed Mas , Shah S.M.N. Nurul , Johari A.T.T. Syed , Rahamathullah Rafizah , Daud I. Adibah and Ma L. Nyuk , Synthesis, Molecular Docking and Biological Activity Evaluation of Alkoxy Substituted Chalcone Derivatives: Potential Apoptosis Inducing Agent on MCF-7 Cells, Anti-Cancer Agents in Medicinal Chemistry 2021; 21 (13) . https://dx.doi.org/10.2174/1871520620999201110190709