Discovery of Promising Sulfadiazine Derivatives With Anti‐Proliferative Activity Against Tumor Cell Lines

ABSTRACT A novel series of pyrimidine sulfonamide derivatives was synthesized through a strategic approach involving the creation of substituted dihydropyrimidinyl‐benzenesulfonamides and subsequent transformation into their chlorinated analogues. These compounds were then subjected to reactions with various amines and phenols, yielding unique substituted sulfapyrimidines. These novel structures integrated essential pharmacophores such as phenols, secondary amines, and benzenesulfonamide moieties, each contributing distinct biological potencies, chemical reactivity, and enhanced pharmacological features. In the pursuit of effective anticancer agents, the newly substituted pyrimidine sulfonamides were characterized using spectroscopic and x‐ray diffraction techniques. The compounds were evaluated for their anti‐proliferative potency against the NCI 60‐cell lines panel, revealing that compound 7c exhibited significant growth inhibition across multiple cancer cell lines. Further assessment through MTT assay on HCT‐116 and MCF‐7 cell lines demonstrated cytotoxicity, while cell cycle analysis of MCF‐7 cells treated with compound 7c revealed arrest at the S phase. Moreover, the effect of 7c on programmed cell death was evaluated using the Annexin V/PI apoptosis assay. The observed promising activity positions these pyrimidine‐based scaffolds as potential candidates for future drug development, offering valuable insights for medicinal chemists engaged in the design and synthesis of anticancer drugs.