Thiophene-based hydrazones and their metal complexes: Synthesis, structure affirmation, antioxidant and cytotoxic activity, photoluminescence, molecular docking, and ADMET studies

This work involves the synthesis of N'-(2‑hydroxy-3‑methoxy-5-nitrobenzylidene)thiophene-2-carbohydrazide (HL1) and N'-(2‑hydroxy-5‑methoxy-3-nitrobenzylidene)thiophene-2-carbohydrazide (HL2) and their complexes with Cu(II), Ni(II), and Fe(II), as well as the investigation of their photoluminescence properties, cytotoxic, and antioxidant activities. Elemental analysis, molar conductivity, FT-IR, UV–Vis, TGA, LC-MS/MS, and 1H and 13C NMR (only for ligands) were used to determine the chemical structures of all compounds. Two complementary tests (CUPRAC and DPPH assays) were used to evaluate the antioxidant activities of the compounds. The results suggested that compound [Fe(L2)2] (L2-Fe) was found to have good radical scavenging power compared to α-tocopherol in the CUPRAC assay. The newly synthesized thiophene-based hydrazones and their metal complexes were screened for in vitro cytotoxic activity assessments against A549 and BEAS-2B cell lines and were found to show high cellular toxicity at lower doses on the A549 cell line. In particular, the Cu(II) complexes ([Cu(L1)2] (L1–Cu) and [Cu(L2)2] (L2–Cu)) exhibited the inhibitory effect against A549 cells with IC50 values of 5.1 and 6.93 μM, respectively. In order to the anticancer and antioxidant effects of the active compounds, the possible interaction mechanisms between novel compounds and target proteins were performed computationally by the molecular docking study. In conclusion, the study provided preliminary information about some biological properties of ligands and their Cu(II) complexes. It revealed that thiophene-based hydrazones may play a crucial role in drug applications. Also compounds that could be drug candidates were compared with both experimental and computational data. © 2025 Elsevier B.V.