Novel sulfonamide-based azo-metal complexes: Synthesis, characterization, theoretical studies, and In Vitro antioxidant and anticancer evaluation

This study reports the synthesis of sulfonamide-based azo-metal complexes [copper (Cu), cobalt (Co), nickel (Ni) and zinc (Zn)], derived from a novel ligand, 3,6-bis(4-hydroxy-3-oxo-5-sulfonamido-phenyl) diazenyl-2,4-dihydroxy-5,7-dioxo-1-benzenesulfonic acid. Fourier-transform infrared spectroscopy, nuclear magnetic resonsance, mass spectrometry, and thermal analysis were used for structural characterization of the synthesized complexes, Elemental analysis confirmed their molecular compositions, while thermogravimetric and differential thermal analysis established their thermal stability. Scanning electron microscopy with energy-dispersive spectroscopy provided surface morphology and elemental distribution and x-ray diffraction analysis suggested the amorphous nature of the complexes. Biological activity evaluation revealed significant antioxidant potential, with the Zn (II) complex exhibiting highest 74% of inhibition (at 25 µg/mL concentration; IC₅₀: 13.44 µg/mL), comparable to standard ascorbic acid (IC₅₀ = 6.80 µg/mL), likely mediated through the Nrf2 pathway. Anticancer activity on the human breast cancer cell line (MCF-7) demonstrated the Ni (II) complex as the most potent agent (IC₅₀ = 8.98 µg/mL at 48 hours) with efficacy close to standard cisplatin (IC₅₀ = 7.23 µg/mL). Molecular docking studies against 17-β-HSD1 enzyme indicated strong binding interactions with Ni (II) complex with the highest docking score (-9.26 kcal/mol). It suggests a potential anticancer mechanism of the complex via the regulation of p53 and PGC1-α pathways, influencing mitochondrial function and glycolysis. HOMO-LUMO energy calculations indicated that Ni (II) and Cu (II) complexes exhibit high reactivity, while the ligand displayed notable stability. The proposed study on the synthesis of azo-metal complexes using 2,4-dihydroxy acetophenone is first of its kind, demonstrating high structural stability and promising anticancer and antioxidant activity, underscoring the need for further research. • Novel bioactive sulfonamide-based azo-metal complexes synthesized and characterized. • Zn(II) complex exhibited highest antioxidant activity, comparable to ascorbic acid. • In vitro cytotoxicity of compounds was evaluated against MCF-7 breast cancer cells. • Molecular docking confirmed azo compounds' interactions with 17-β-HSD1 active sites.