Design, synthesis, and biological evaluation of thiophene-based thiosemicarbazones and their Cu(II), Ni(II), Zn(II) complexes

The research includes the synthesis and characterization of several new thiosemicarbazone ligands and complexes. These ligands were functionalized with pyrrolidine and morpholine substituents after being generated from thiophene-3-carboxaldehyde. UV–Vis, FTIR, NMR, elemental analysis, and mass spectrometry were used to produce and analyze the corresponding dimeric Cu(II), Ni(II), and Zn(II) complexes. The electronic structure, molecule electrostatic potential, and HOMO–LUMO energies were revealed by Density Functional Theory simulations (B3LYP/LANL2DZ), suggesting their potential for bioactivity.Steady-state and synchronous photoluminescence spectroscopy assessed the interaction with bovine serum albumin (BSA); results displayed significant quenching and microenvironmental changes near Trp-212. Cyclic voltammetry electrochemical studies uncovered quasi-reversible metal-centered redox processes in the Cu(II) complexes.Lastly, initial in vitro anticancer studies (MTT) on MDA-MB-231, T24 and MCF-10a cell lines showed significant cytotoxicity, especially for copper complexes, with low micromolar IC₅₀ values.SwissADME was employed to evaluate the molecules' pharmacokinetic traits and drug-likeness, revealing favorable lipophilicity, solubility, and bioavailability. Molecular docking against EGFR showed strong binding affinities (ΔG = −8.6 to −9.8 kcal/mol), reinforced by specific hydrogen bonds and π–π interactions. Ethidium bromide displacement fluorescence tests indicated intercalative and groove-binding modes with binding constants in the 104–105 M−1 range, confirming binding to calf thymus DNA.These thiophene-based metal complexes are shown to be interesting candidates for additional development as metal-based anticancer medicines by this multi-technique study.