Synthesis, characterization, and anticancer potency of coumarin-derived thiosemicarbazones and their Copper(II) complexes

[Display omitted] •Coumarin Thiosemicarbazones: acidic hydrogen at N(1) involved in intramolecular hydrogen bonding with lactone carbonyl forming more stable E isomer than Z isomer.•Cu(II) complex: distorted square planar, carbonyl O, imine N, thiolate S−, and Cl− ion coordinated.•In Vitro: anticancer activity in dose dependent manner against MCF-7 and MDA-MB-231 cells.•In Silico: follows Lipinski’s rule and high binding energy (−5.8 to −8.0 Kcal/mol) against EGFR and HER-2. A series of 3-acetylcoumarin-based thiosemicarbazones and their copper(II) complexes were synthesized and characterized by elemental analysis, IR, UV–Vis, HR-ESI Mass, NMR, EPR and single crystal XRD. The XRD study revealed thione tautomer for TSCs 3 (AcCmDEtTSC) and 4 (AcCmDPrTSC) whereas Cu(II) complex 8[Cu(AcCmDPrTSC)Cl] has distorted square planar geometry around the metal ion. Compound 1 (AcCmMeHTSC) among the thiosemicarbazones (TSCs) was more effective against both breast cancer cell lines: MCF-7 (IC50; 13.02 µg/mL) and MDA-MB-231 (IC50; 42.71 µg/mL), whereas compounds 7[Cu(AcCmDEtTSC)Cl] (IC50; 32.84 µg/mL) and 8[Cu(AcCmDPrTSC)Cl] (IC50: 34.69 µg/mL) among the Cu(II) complexes were more effective against MDA-MB-231 cell lines. Anticancer activity of the test compounds enhanced in dose dose-dependent manner against both MCF-7 and MDA-MB-231 cells. Molecular docking study showed significant binding affinity of the test compounds, notably compound 2 (AcCmEtHTSC) with −7.1 kcal/mol and −8.0 kcal/mol, compound 3 with −7.3 kcal/mol and −7.8 kcal/mol against target proteins EGFR and HER2 respectively. Although the IC50 value of the synthesized compounds is not very encouraging, their significant binding affinity values (−5.8 kcal/mol to −8.0 kcal/mol) against the target proteins EGFR and HER 2 is encouraging for the further exploration of their anticancer activity in the future.