Introduction: Chalcones are important α, β-unsaturated carbonyl compound scaffolds in medicinal chemistry because of their structural simplicity and diverse biological activities, especially their anticancer potential. Developing environmentally friendly and efficient synthetic methods for chalcone derivatives remains a key research goal. Methods: An eco-friendly, one-pot synthetic substituted chalcone derivatives using Amberlyst® 15 as a reusable heterogeneous acid catalyst in water. The aldol condensation between substituted benzaldehydes and acetophenones was carried out under mild conditions (60-70°C). All synthesized compounds were characterized by LC-MS, 1H, and 13C NMR spectroscopy. Molecular docking studies were performed against the PARP protein (PDB ID: 3GEY), and the most promising compound was further evaluated for in vitro cytotoxicity using the MTT assay on MCF-7 breast cancer cells. results: For the objectives of our investigation and the optimization of reaction conditions, we first focused on the selective formation of (E)-3-(2-ethoxy-5-(methylthio)phenyl)-1-(4-fluorophenyl)prop-2-en-1-one (1aa), achieved by combining the benzaldehyde derivative 1a and benzophenone 1b. The optimization process involved varying the type and Amberlyst® 15 Ion Exchange Resin as an Acid Catalyst, Water as a green solvent, and their equivalents, while maintaining a reaction temperature of 60-70°C for 24 hours. Results: The developed methodology afforded chalcone derivatives in excellent yields of up to 95%, with simple work-up, catalyst recyclability, and elimination of hazardous solvents. Docking studies revealed that compound 1aa exhibited the strongest binding affinity toward PARP (-9.099 kcal/mol), surpassing the reference drug Niraparib (-7.825 kcal/mol). In vitro evaluation showed that compound 1aa displayed moderate cytotoxic activity against MCF-7 cells with an IC50 value of approximately 18 µM and significantly reduced intracellular reactive oxygen species levels. Discussion: The findings demonstrate the efficiency of Amberlyst® 15 as a green catalyst and highlight the role of substituent effects in enhancing biological activity. Conclusion: In summary, a green and efficient one-pot synthetic method for chalcone derivatives was successfully developed using Amberlyst® 15 as a reusable solid acid catalyst under aqueous conditions.
Savaliya et al. (Fri,) studied this question.