Synthesis of New 1,4-dihydropyrimidine Derivatives, Breast Cancer Anticancer, and In-silico Studies

Abstract

This study reports a sustainable and environmentally friendly approach for the synthesis of novel pyrimidine Schiff base derivatives through a multicomponent grinding reaction conducted at room temperature under solvent-free conditions. The synthesis involved pyrimidine, various aldehydes, and p-toluenesulfonic acid as a catalyst. The obtained compounds (1–3) were evaluated for their potential anticancer activity against the breast cancer estrogen receptor alpha (ERα). Structural characterization was carried out using FT-IR, NMR spectroscopy, mass spectrometry, and elemental analysis. In addition, molecular docking studies were performed to investigate the binding interactions of the synthesized 1,4-dihydropyrimidine-5-carboxylate derivatives (1–3) with the ERα protein. Among the tested compounds, derivative (3) demonstrated the most promising biological activity, exhibiting an IC₅₀ value of 8.91 μg/L compared with cisplatin (cis-Pt) as the reference drug, along with the highest binding affinity toward ERα. These findings suggest that compound (3) may serve as a promising lead candidate for breast cancer therapy. Molecular modeling studies were conducted using the Molecular Operating Environment (MOE 2019) software, while toxicity prediction was performed using Osiris software.