2-Pyridone Scaffold as A Precursor for Different Nitrogen-Containing Compounds: Synthesis, In Vitro Anticancer Evaluation, and Molecular Docking

Research into breast cancer treatments is progressing and contemporary, particularly with a focus on tyrosine kinase receptors, which are crucial for regulating various cellular functions. The chemistry of the 2-pyridone scaffold allows for the creation of diverse molecular structures. Converting 2-pyridone into a hydrazide form enhances its biological activity. Using polyphosphoric acid enables effective electrophilic attacks, resulting in various polycyclic compounds as naphthyridine and pyridopyrimidine. These compounds are being evaluated as potential tyrosine kinase inhibitors, refined through the "rule of five" to improve their drug-like properties. In assessing their cytotoxicity, the MTT assay was performed on MCF-7 cell lines using different concentrations. Compounds 2, 4, 8, 10, 12, and 16 have demonstrated notable IC50 values, surpassing the efficacy of doxorubicin, which has an IC50 value of 11.86 µM. Among these compounds, 2, 4, and 8 are particularly distinguished by their favorable molecular docking simulation profiles. These compounds represent promising candidates for further investigation in the treatment of breast cancer.