Ligands of the 3-hydroxy-4-pyridinone type are considered as privileged molecules with well-known applications such as:

  • Anti-microbial drugs

  • Anti-diabetic agents

  • Iron deficiency chlorosis correctors

  • Fluorescent probes for diagnosis

  • Chromogenic reagents for metal ion determination in natural waters

  • Tyrosinase inhibitors

As a common feature, these ligands are excellent chelators to a wide range of metal ions, which are essential nutrients for most living organisms, playing a vital role in defining their physiological state. Thus, maintenance of metal ion homeostasis is determinant for health and its disruption causes severe disorders and diseases. Therefore, to assess metal ion concentrations and to monitor their traffic within cells and body fluids is crucial to understand therapeutic targets and drug design.

Research is focused on the design of chelators, particularly 3-hydroxy-4-pyridinones, that may be of used, amongst others, as novel therapeutic strategies to fight Infection and Diabetes. The first is related with a particular interest in Iron Biology and with the antibacterial effect of cooper complexes, and the second with the potential insulin-like effect of Zinc and Vanadium complexes. The design of metal ion chelators is the common factor. In the first diseases the drug is the chelator itself or copper chelates, while in the second the drug is a metal-chelate. The potential of these ligands as tyrosinase inhibitors may be associated with their ability to chelate copper ions, thus inactivating the enzyme. The design of fluorescent chelators that allow visualization of their pathways within the cell and the study of their interaction with metal ions is also an object of research.


A combined experimental and computational study to discover novel tyrosinase inhibitors. Amaral, L. M. P. F., Moniz, T., Leite, A., Oliveira, A., Fernandes, P., Ramos, M.J., Araújo, A. N., Freitas, M., Fernandes, E., Rangel, M., Journal of Inorganic Biochemistry, 2022, 234, 111879; https://doi.org/10.1016/j.jinorgbio.2022.111879

Antibacterial activity of naphthyl derived bis-(3-hydroxy-4-pyridinonate) copper(II) complexes against multidrug-resistant bacteria. Leite A., Bessa L.J., Silva A.M.G., Gameiro P., de Castro B., Rangel M., Journal of Inorganic Biochemistry, 2019, 197, 110704; https://dx.doi.org/10.1016/j.jinorgbio.2019.110704

Tuning anti(myco)bacterial activity of 3-hydroxy-4-pyridinone chelators through fluorophores. Maria Rangel, Tânia Moniz, André M. N. Silva, Andreia Leite, Pharmaceuticals, 2018, 11, 110; https://dx.doi.org/10.3390/ph11040110

EPR and 51V NMR studies of prospective anti-diabetic bis(3-hydroxy-4-pyridinonato) oxidovanadium(IV) complexes in aqueous solution and liposome suspensions. Ferreira, S., Leite, A.*, Moniz, T., Andrade, M., Amaral, L.M.P.F., de Castro, B., Rangel, M.*, New Journal of Chemistry, 2018, 42, 8088-8097; https://doi.org/10.1039/C7NJ04678B

Investigation of the insulin-enhancing properties of Zinc(II) 3-hydroxy-4-pyridinone complexes: identification of a new compound with a hypoglycemic effect in type I-like diabetic animals. Moniz, T., Amorim, M.J., Ferreira, R., Nunes, A., Silva, A.M.G., Queirós, C., Leite, A., Gameiro, P., Sarmento, B., Remião, F., Yoshikawa, Y., Sakurai, H. and Rangel, M., Journal of Inorganic Biochemistry, 2011, 105, 1675–1682; http://dx.doi.org/10.1016/j.jinorgbio.2011.09.005