Abstract
AIM: The chalcone scaffold pyrazole is important in organic and medicinal chemistry. This study presents the design and synthesis of new chalcone-coupled pyrazole derivatives (1a-1o). The new compounds were characterized using FT-IR, (1)H-NMR, (13)C-NMR, GC-MS, elemental analysis, and cytotoxic analysis on MCF-7 and HepG2 cancer cell lines. The synthesized compounds also underwent molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and DFT (density functional theory) studies. RESULTS: Compound 1a showed high cytotoxic activity against MCF-7 cells (LC(50), 0.62 ± 0.01 µM), outperforming standard Doxorubicin. Compounds were examined using molecular docking, ADME-T, and DFT calculations. Compound 1a had a higher binding affinity (-10.8 Kcal/mol) than Doxorubicin (-4.7 Kcal/mol). ADME-T profile and pharmacokinetic predictions were performed on the analogs. DFT with the B3LYP/6-311++G (DP) basis set helped determine optimal shape and dimensions. Additional Gaussian 16-based DFT calculations were conducted on compounds (1a-1o). The HOMO-LUMO analysis revealed compound 1a had a significant energy gap (2.5056 eV, from -7.94026 eV to -5.43465 eV). CONCLUSION: Compound 1a may be a promising anti-cancer agent.