The present work was aimed to synthesize novel chromone derivatives to target estrogen receptor positive breast cancer. About 80% of all breast cancers are “ER-positive. The chromone scaffold is a privileged scaffold for exploration of anticancer agents. 3(4-oxo-4H-chromen-3-yl)acrylic acid amides derivatives designed, synthesized by employing the molecular hybridization approach between different aromatic, aliphatic amines and 3(4-oxo-4H-chromen-3-yl)acrylic acid. The docking study of 3(4-oxo-4H-chromen-3-yl)acrylic acid amides were performed using Schrodinger 2015 (maestro 10.1) on human estrogen receptor ï¡-Ligand-Binding domain (1XP6), Tyrosyl-t-RNA synthetase protein (1JIK), DNA gyrase protein (4DUH), nitric oxide synthase (3NLE) and evaluated in vitro antioxidant activity, antibacterial activity, cytotoxicity against human Breast Cancer Cell Line (MCF-7). The in silico studies indicated that 3(4-oxo-4H-chromen-3-yl)acrylic acid amides derivatives exhibited comparable docking score and good hydrogen bond interactions with the amino acids present in the active site of 3NLE and 1XP6. Many of the synthesized compounds exhibited potent antioxidant and cytotoxic activity. The most potent antioxidant activity was observed for compound A5 with IC50 value of 0.5 μg/ml, most potent anticancer activity was observed for compound A1 with IC50 value of 37.13 μg/ml and potent antibacterial activity was observed for compound A1 with Minimum Inhibitory Concentration (MIC) value of 100 μg/ml against Escheriea coli and Proteus vulgaris.