Design, Synthesis, and Molecular Docking of Pyrido[3,4‐ <i>d</i> ] Pyrimidine Derivatives: Unveiling Their Anticancer Potential

Abstract A bicyclic nitrogen‐containing compound, pyrido–pyrimidine and its derivatives are an important class of heterocycles due to a broad spectrum of biological as well as pharmaceutical applications. Considering its potential medicinal applications, two series of evolving scaffolds Pyrido[3,4‐ d ] pyrimidine derivatives were synthesized and evaluated for their efficacy as anticancer agents. Overall, 15 molecules were synthesized through the condensation of 3‐amino isonicotinamide with various cinnamaldehydes at two different temperatures 60 °C and 120 °C in dimethyl sulfoxide (DMSO) solvent. Temperature played a significant role to obtain two different series, that is, Pyrido[3,4‐ d ] pyrimidine and its reduced form dihydropyrido[3,4‐ d ] pyrimidine derivatives. All the synthesized compounds were characterized using IR, NMR ( 1 H and 13 C) spectroscopy and mass spectrometry. The anticancer potential of synthesized molecules was examined in vitro against three different cell lines, that is, Human lung cancer ( A‐549 ), breast cancer ( MCF‐7 ) and Monkey Normal Kidney Epithelial Cell Line ( Vero ). The outcomes indicated that compounds 4d and 5d had potential promising anticancer agent, showing GI 50 values 3 × 10 −5 and 5 × 10 −5 for A‐549 cell lines whereas 3 × 10 −6 and 5 × 10 −5 against MCF‐7 and 2 × 10 −5 /9 × 10 −2 toward kidney epithelial cell lines, respectively. To support this observation, a three‐way ANOVA was performed, and the estimated marginal means offered valuable insights into the comparative activity profiles.