Synthesis, characterization, biological screening and in silico studies of novel pyrazole-chalcone derivatives as potent aromatase inhibitors for breast cancer therapy

Abstract Background Chalcone derivatives, which are known for their non-steroidal anticancer properties, have been extensively studied. One potential application of chalcone is as aromatase inhibitors, a crucial strategy for treating estrogen receptor-positive (ER +) breast cancer. Thirteen chalcone derivatives were synthesized via the aldol condensation method, and their structural properties were characterized using FTIR, MS, and NMR. Molecular docking was performed using the Schrodinger Suite, and the QikProp program was used for in silico ADME analysis. Results The cytotoxicity of all 13 synthesized compounds was evaluated using the MCF-7 human cancer cell line. Additionally, specific chalcone derivatives were subjected to further aromatase inhibition testing. Four compounds, namely 3a, 3c, 3g, and 3h demonstrated significant potency, with IC 50 values of 20.66 ± 1.79 µM, 14.66 ± 1.09 µM, 17.96 ± 1.57 µM, and 15.52 ± 1.25 µM, respectively. Further analysis using a fluorogenic assay revealed that compounds 3a, 3c, 3g, and 3h exhibited in vitro aromatase inhibitory activities with IC 50 values of 4.684 ± 3.33 µM, 1.368 ± 0.90 µM, 2.124 ± 0.83 µM, and 3.314 ± 0.6123 µM, respectively. The ADME parameters of the synthesized compounds were also computed using QikProp 5.1 software. Conclusions Compound 3c emerged as the most potent aromatase inhibitor, with an IC 50 value of 1.368 ± 0.90 µM, surpassing that of letrozole. Compounds 3g and 3h also exhibited strong aromatase inhibitory activities. These findings suggest that 3c, 3g, and 3h are promising lead compounds for further research as potential anticancer agents, particularly in the context of aromatase inhibition.