Synthesis, characterization, anticancer activity, molecular docking and DFT calculation of 3-acetylcoumarin thiosemicarbazones and Schiff’s bases

• Thiosemicarbazones (3a-d) of 3-acetylumbelliferone and Schiff’s bases (4a-b) of 3-acetylcoumarin were synthesized and characterized by elemental analysis, UV–Vis, IR, NMR, and HR MS. • The compounds exhibited potent preferential inhibition effects against the MCF-7 cell line, with IC 50 in the range of 147.8–505.1 µg/mL. • The compound 3c showed a higher proportion of cells in G1 (37.21%) and S (26.86%) phases and a lower proportion of cells in G2 phase (26.37%), with respect to control. • Molecular docking with target proteins VEGFR2 and EGFR demonstrated their significant binding interactions with the key residues compared to the reference drug erlotinib. • DFT analysis revealed effective reactivity of the synthesized compounds due to low band gap energy of HOMO and LUMO relative to the reference drug, erlotinib. The new thiosemicarbazones (3a-d) of 3-acetylumbelliferone and Schiff’s bases (4a-b) of 3-acetylcoumarin were synthesized, characterized by elemental analysis, UV–Vis, FT-IR, NMR, and ESI-HR MS, and evaluated for their anticancer potency against the human breast cancer (MCF-7) cell line. All the tested compounds exhibited good to moderate anticancer efficacy in a dose-dependent manner. The synthesized compounds exhibited potent preferential inhibition effects against the MCF-7 cell line, with IC 50 range of 147.8–505.1 µg/mL. The most potent compound, ( E )-N-(1-(7-hydroxy-2-oxo-2 H -chromen-3-yl) ethylidine)-2,6-dimethylmorpholine-4-carbothiohydrazide (3c) , showed significant cytotoxicity with an IC 50 value of 147.8 µg/mL against the tested cell line. It showed a higher proportion of cells in G1 (37.21 %) and S (26.86 %) phases and a lower proportion of cells in G2 phase (26.37 %), with respect to control. Molecular docking of all the synthesized compounds with target proteins VEGFR2 and EGFR demonstrated their significant binding affinity and interactions with key residues compared to the reference drug (erlotinib). DFT-based analysis showed that all the compounds have effective reactivity due to the low band gap energy of HOMO and LUMO relative to the reference drug, erlotinib (4.26 eV). The reactivity-related quantum mechanical parameters η, S, χ, μ, and ω indicated that these compounds have a high efficacy towards the target enzymes VEGFR2 and EGFR. All of the synthesized compounds had drug-like action, according to ADMET predictions.