This study reports the synthesis, characterization, DFT calculations and in vitro antimicrobial, cytotoxic and antiproliferative evaluation of La(III), Eu(III), and Gd(III) metal complexes with ampicillin. The compounds were characterized by Thermal Gravimetric Analysis (TGA), elemental analysis, ultraviolet–visible spectroscopy (UV–Vis), Fourier-transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (¹H NMR), indicating a 2:1 metal-to-ligand ratio with ampicillin, and likely, a coordination through carbonyl, carboxylic and β-lactam groups, with the general formula [Ln₂(L)(Cl)₅(H₂O)_x] (Ln = La(III), Eu (III), Gd (III), and x = 2 for La(III), 5 for Eu(III) and Gd(III), L-ampicillin anion). Antimicrobial studies showed activity against ampicillin-resistant Staphylococcus aureus (MIC = 15.6 µg·mL⁻¹) but no activity against Escherichia coli. In cytotoxicity studies, all complexes inhibited B16-F10 (murine melanoma) proliferation, with GI₅₀ values around 140 µg·mL⁻¹. Against U251 (glioma) cell line, only [Eu₂(L)(Cl)₅(H₂O)₅] exhibited cytotoxicity activity, GI₅₀ = 104 µg·mL⁻¹, and notably, [Eu₂(L)(Cl)₅(H₂O)₅] was active against MCF7 (breast carcinoma) with a GI₅₀ = 8.1 µg·mL⁻¹. However, all complexes exhibited high cytotoxicity in NIH-3T3 cells (GI₅₀ = 0.030–2.90 µg·mL⁻¹), indicating limited selectivity between normal and cancer cells. Nevertheless, except for the La complex, most compounds were less cytotoxic than doxorubicin, highlighting the need for further optimization to improve selectivity.

This work studies the synthesis of complexes using chlorambucil (La-CLA) as a ligand and lanthanum as a metallic center, in order to enhance their biological activities. The compounds produced were characterized by infrared spectroscopy and 13C and 1H nuclear magnetic resonance; the results obtained indicate that coordination bonds formed between the ligands and that La3+ was present in a bidentate way through carboxylic groups in the complexes. Elemental and thermogravimetric analyses indicate that the stoichiometry obtained for chlorambucil complexes was a 2:1 ligand:metal ratio. The anticancer activity assays indicated that the La-CLA complex showed better activity than the ligands against the cell lines K562 (Chronic Myeloid Leukemia), HT-29 (Colorectal Cancer), Caco 2 (Human Colorectal Adenocarcinoma) and B16-F10 (Murine Melanoma), with GI50 values in the range of 0.31–31.86 μM. The La-CLA complex showed a selectivity index (SI) equal to 15.64 for the K562 cell line with respect to normal J774 cells (murine macrophages).