Synthesis and biological evaluation of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates

[Display omitted] •Uniting chromene, pyrimidine & phosphonate has augmented novelty to the compounds.•The molecular property study has optimized C1 symmetry & triviality to the compounds.•Shown potential inhibition against A549, DU-145, PC-3, HeLa, & MCF-7 cell lines.•Effectively bound with Histidine residues of 3QJZ, 3VHE, 3V49, 3F81, & 3R7Q proteins.•SAR study has revealed title compounds as potential histidine amino acid inhibitors. This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10–30 μM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa), & 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery.