Synthesis, characterization, and biological evaluation of mixed-ligand zinc(II) acesulfame-amine complexes

Eight novel mixed-ligand zinc(II) complexes with acesulfame (acs⁻) and amine co-ligands (aminopyridine, aminomethylpyridine, aminobenzothiazole, and aminopyrimidine derivatives) were synthesized and characterized. In most complexes, acesulfame coordinated as monodentate via the ring nitrogen, except for [Zn(acs)₂(ampy)₂], where binding likely occurred through the carbonyl oxygen. Antibacterial screening against Staphylococcus aureus , Streptococcus pneumoniae (Gram-positive), and Escherichia coli (Gram-negative) revealed that [Zn(acs)₂(capy)₂] produced the largest inhibition zones across all strains. Notably, [Zn(acs)₂(cabt)₂] demonstrated high inhibition efficacies (86%, 83%, and 84%) with inhibition zones of 24, 20, and 26 mm against S. aureus , S. pneumoniae , and E. coli , respectively. Cytotoxicity assays against human cancer cell lines showed that [Zn(acs)₂(abt)₂] was most potent against MCF-7 breast cancer cells (IC₅₀ = 49.34 ± 1.87 μM), while [Zn(acs)₂(mabt)₂] was most effective against HepG2 liver cancer cells (IC₅₀ = 39.45 ± 1.72 μM). Molecular docking studies using Auto-Dock Vina tool identified complexes 6 , 7 , and 8 as promising candidates for further investigation, exhibiting more negative binding energies, favorable structural fits, and low RMSD values (< 2 Å) compared to the reference antibiotic streptomycin.