Daphnetin Hydrazones – Synthesis and Screening of Anti-proliferative Potential Against Human Breast Cancer

Abstract

Six new hydrazones of 3-acetyldaphnetin were synthesized from 3-acetyldaphnetin (1) with different hydrazides and were tested for anti-proliferative activity against the human breast cancer cell line MCF-7 using an MTT assay. These hydrazones were computationally evaluated for ADMET and drug-likeness studies using online tools. Molecular docking methodology was applied to study the mode of interaction between the estrogen receptor (PDB ID: 3ERT), progesterone receptor (PDB ID: 3G8O), and human epidermal growth factor receptor 2 (HER2) (PDB ID: 3PP0). All the compounds showed promising anti-proliferative activity against the MCF-7 cell line, with IC50 values ranging from 5.76 to 32.45 µM. The ADMET properties of the compound 2c were determined, and this compound had accurate pharmacokinetic profiles. This hydrazone possesses good ADMET properties and showed drug-like properties with a strong affinity towards HER2, evidenced by its high binding energy compared to the other two targets. © 2025 by the authors.