Metallodrugs for Neglected Tropical Diseases

Published by Camilla Abbehausen

January 23, 2024

Summary

The World Health Organization (WHO) identifies Neglected Tropical Diseases (NTDs) as infections caused by helminths, protozoa, bacteria, fungi, viruses, and ectoparasites, prevalent in underdeveloped regions lacking access to clean water and sanitation. The WHO, in collaboration with the Pan American Health Organization (PAHO), has set ambitious goals for 2021-2030, including a 90% reduction in interventions for NTDs, a 75% decrease in disability-adjusted life years, and the elimination of at least one NTD in 100 countries.

Metallic complexes, known as coordination compounds, involve a central metallic atom linked to ligands via coordination bonds. Organometallic chemistry, a subarea of coordination chemistry, introduces compounds with metal-carbon bonds, allowing for ligand and metal rearrangements. These compounds have been utilized for medicinal purposes since ancient times, with notable examples like bismuth subsalicylate and cisplatin.

The treatment of challenging diseases such as leishmaniasis, arboviruses, and emergent viruses presents opportunities for metallodrugs. In our project, we design and study metal complexes as potential candidates for more effective treatments than current pharmaceuticals, bridging the gap between organic and inorganic chemistry for innovative medical solutions.

Research Outcomes

(1) Rosa, L. B.; Galuppo, C.; Lima, R. L. A.; Fontes, J. V.; Siqueira, F. S.; Júdice, W. A. S.; Abbehausen, C.; Miguel, D. C. Antileishmanial Activity and Insights into the Mechanisms of Action of Symmetric Au(I) Benzyl and Aryl-N-Heterocyclic Carbenes. J. Inorg. Biochem. 2022, 229, 111726. https://doi.org/10.1016/j.jinorgbio.2022.111726.

(2) Fontes, J. V.; Santos, I. A.; Rosa, L. B.; Lima, R. L. A.; Jardim, A. C. G.; Miguel, D. C.; Abbehausen, C. Antileishmanial and Anti-Chikungunya Activity of Cu(I)-N-Heterocyclic Carbenes. ChemistrySelect 2022, 7 (31), e202201560. https://doi.org/10.1002/slct.202201560.

(3) Aires, R. L.; Santos, I. A.; Fontes, J. V.; Bergamini, F. R. G.; Jardim, A. C. G.; Abbehausen, C. Triphenylphosphine Gold(I) Derivatives Promote Antiviral Effects against the Chikungunya Virus. Metallomics 2022, 14 (8), mfac056. https://doi.org/10.1093/mtomcs/mfac056.

(4) Rosa, L. B.; Aires, R. L.; Oliveira, L. S.; Fontes, J. V.; Miguel, D. C.; Abbehausen, C. A “Golden Age” for the Discovery of New Antileishmanial Agents: Current Status of Leishmanicidal Gold Complexes and Prospective Targets beyond the Trypanothione System. ChemMedChem 2021, 16 (11), 1682–1696. https://doi.org/10.1002/cmdc.202100022.

(5) dos Santos Oliveira, L.; de Souza Guarda, P. H.; Rosa, L. B.; Rodrigues, G. C.; Affonso, D. D.; de Carvalho, J. E.; Santos, I. A.; Harris, M.; Nakahata, D. H.; Sabino, J. R.; Miguel, D. C.; Tasca Gois Ruiz, A. L.; Gomes Jardim, A. C.; Abbehausen, C. Exploring the Copper(II) Coordination to 2’-Hydroxy-4-Benzyloxychalcone Analogues and Their Potential Pharmacological Applications. Inorganica Chimica Acta 2023, 121806. https://doi.org/10.1016/j.ica.2023.121806.

(6) Oliveira, L. S.; Rosa, L. B.; Affonso, D. D.; Santos, I. A.; da Silva, J. C.; Rodrigues, G. C.; Harris, M.; Jardim, A. C. G.; Nakahata, D. H.; Sabino, J. R.; de Carvalho, J. E.; Miguel, D. C.; Ruiz, A. L. T. G.; Abbehausen, C. Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity. ChemBioChem n/a (n/a), e202300696. https://doi.org/10.1002/cbic.202300696.

(7) Rodrigues, G. C.; Barrionuevo, M. V. F.; San-Miguel, M. A.; Abbehausen, C. Unraveling Ligand Exchange Reactions in Linear Neutral Au(I) and Cu(I) N-Heterocyclic Carbene Complexes for Biological Applications. New J. Chem. 2024, 48 (5), 2040–2047. https://doi.org/10.1039/D3NJ04945K.

Supported by

FAPESP

CNPq

CAPES