Structural and spectroscopic analysis and evaluation of cytotoxic activity of 2-hydroxychalcones against human cancer cell lines

• Four chalcones were synthesized by Claisen-Schmidt condensation reaction. • DFT calculations presented a good agreement with the experimental data. • Spectroscopic proprieties of the chalcones depend on the substitution on the B-ring. • Anticancer activity was observed against HCT-116 and HL-60 tumor cell lines. Chalcones and their derivatives exhibit a broad spectrum of pharmacological activities, including antiproliferative activities. Accordingly, they are deemed robust anticancer candidates for cytotoxicity assays. Herein, we synthesized and characterized four chalcones using nuclear magnetic resonance ( 1 H NMR and 13 C NMR), Fourier transform Raman (FT-Raman), attenuated total reflection Fourier transform infrared (ATR-FTIR), and ultraviolet-visible (UV–vis) spectroscopy. Theoretical calculations of quantum chemistry were performed to obtain data regarding normal vibration modes, frontier molecular orbitals, molecular electrostatic potential maps, theoretical UV–vis spectra, and quantum chemical parameters expected for these chalcones. In addition, we evaluated the cytotoxic potential of these compounds. For synthesized compounds, quantum chemical calculations demonstrated excellent correlation with experimental data. The electronic properties revealed that chalcones 1 and 4 possess a higher electrophilic character, while chalcones 2 and 3 possess a higher nucleophilic character. Chalcone 3 demonstrated the highest value of HOMO energy, indicating the greatest propensity to donate electronic density among the four compounds. According to the HOMO-LUMO energy gap and global hardness, the reactivity of chalcones should follow the order 1 < 2 < 4 < 3. Regarding the cytotoxic potential, chalcones 1 and 4 exhibited superior activity against HL-60 acute promyelocytic leukemia cells (IC 50 = 14.09 ± 1.001 and 28.02 ± 1.47 µM, respectively) and HCT-116 colon cancer cells (IC 50 = 22.64 ± 0.64 and 42.74 ± 4.63 µM, respectively).