Bioactive molecules with potential application as antimicrobial and antifungal agents containing fragments of natural compounds or drugs

Two new thiosemicarbazones were synthesized: 5-bromo-2-hydroxybenzaldehyde 4-(4- acetamidophenyl)thiosemicarbazone (H₂L¹) and 3,5-dibromo-2-hydroxybenzaldehyde 4-(4- acetamidophenyl)thiosemicarbazone (H₂L^₂). These substances were characterized using physicochemical methods, including ¹H and ¹³C NMR spectroscopy, FTIR, melting point determination, and retention factor measurement. Based on the obtained thiosemicarbazones, 16 coordination compounds of copper(II), nickel(II), cobalt(III), and iron(III) were synthesized. Metal content analysis was performed, and the composition of the complexes was determined as follows:  [Cu(HL^1,2)(H₂O)]X  (X=Cl^-,  Br^-,  NO₃^-,  ClO₄^-),  [Cu(L^1,2)H₂O],  [Ni(HL^1,2)₂]; [M(HL^1,2)₂]NO₃ (M = Co³⁺, Fe³⁺). The measured molar electrical conductivity values ranged from 46 to 68 Ω⁻¹·cm²·mol⁻¹, corresponding to 1:1 electrolytes.  Coordination compounds [Cu(L^1,2)H₂O], [Ni(HL^1,2)₂] are non-electrolytes (λ=3-5 Ω^-1•cm²•mol^-1). FTIR spectra analysis for the synthesized coordination compounds confirms that the thiosemicarbazones act as tridentate ligands coordinating to the metal via ONS donor atoms.
For theantimicrobial activity of the coordination compounds was studied against Gram-positive microorganisms (Staphylococcus aureus and Bacillus cereus), Gram-negative microorganisms (Escherichia coli and Acinetobacter baumannii), and antifungal activity against Candida albicans, Candida krusei and Cryptococcus neoformans. The results showed that the synthesized compounds are more active against Gram-positive microorganisms. Copper(II) compounds with 4-(4-acetamidophenyl)thiosemicarbazone 5-bromo-2-hydroxybenzaldehyde exhibited higher activity than nickel(II) compounds with the same ligand. The activity of the complexes is also influenced by the nature of the acidic residue. The activity increases as follows: for copper(II) complexes with H₂L¹: Br^- ≈ NO3^- > ClO₄^-, and for copper(II) complexes with H₂L²: NO₃^- > ClO₄^- > Br^- > Cl^-. The complexes [Cu (HL1)(H2O)]Br and [Cu (HL¹)(H₂O)]NO₃ were found to be more active against tStaphylococcus aureus than tetracycline, a broad-spectrum antibiotic widely used in medicine.