Some poly functionalized heterocyclic‐compounds containing pyridine‐moieties were readily assembled by combining differently functionalized pyridopyrimidine‐6‐carbonitrile derivatives 1a,b with different electrophilic and nucleophilic reagents via short synthetic routes. The structures of the prepared derivatives were ascertained from their‐spectral‐and elemental analyses. Some of the synthesized compounds were tested as plausible antitumor agents. Most of those tested compounds likes 7, 9, 10, 11a showed cytotoxic potencies against different tumor cell lines. In addition, the assessments for their antioxidant activities have also been done and compound 9 exhibited the highest antioxidant activity while compounds 7 and 10 showed moderate activities. Finally, molecular docking studies were carried out which favorably indicated a high support for the experimental‐results.

N methylene]-2-cyanoacetohydrazide (3) was synthesized in excellent yield from the condensation of 4-Chloro-2-oxo-2H-chromene-3-carbaldehyde with cyanoacetohydrazide. Compound 3 was utilized as a building block to synthesize novel coumarin and heterocyclefused coumarin derivatives. The chemical structures of all the new coumarin compounds were identified by spectral analyses. Some of the new coumarins compounds were screened in human cancer cell lines (HEPG-2, MCF-7, HCT-116 and PC-3) to learn about their cytotoxic effects in addition to the study of their DNA damage and antioxidant activity. Three of these compounds exhibited remarkable antioxidant and anti-proliferative activities. Moreover, they have the capability to protect DNA from damage induced by bleomycin. Molecular docking, DFT and molecular electrostatic potential studies were performed on the compounds in vitro.[a] M. A.