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
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