Synthesis, cytotoxicity, and molecular docking studies of novel 2-amino-4-aryl-pyrano[2,3-b]indolizine-3-carbonitrile derivatives

This study aimed to synthesize 2-amino-4-aryl-pyrano[2,3-b]indolizine-3-carbonitrile derivatives from 1-phenylindolizine-2-one and evaluate their in vitro cytotoxic potential. Compounds 4a–p were prepared via condensation with aromatic aldehydes and malononitrile, and their cytotoxicity was tested against MCF-7, A549, and 3T3 cells using the MTT assay, followed by DNA-fragmentation analysis of the most active derivatives. Several compounds showed marked cytotoxicity within the tested concentration range (3.91–500 µg/mL), and active derivatives induced DNA fragmentation consistent with apoptosis. Docking studies identified comparatively favorable predicted interactions with tubulin, particularly for compound 4f . However, these computational findings represent preliminary binding hypotheses and require experimental validation.