Abstract
Leishmaniasis, a neglected tropical disease caused by protozoans of the genus Leishmania, kills around 20–30 thousand people in Africa, Asia, and Latin America annually and, despite its potential lethality, it can be treated and eventually cured. However, the current treatments are limited owing to severe side effects and resistance development by some Leishmania. These factors make it urgent to develop new leishmanicidal drugs. In the present study, three ruthenium(II) organometallic complexes containing as ligands the commercially available anti-inflammatories diclofenac (dic), ibuprofen (ibu), and naproxen (nap) were synthesized, characterized, and subjected to in vitro leishmanicidal activity. The in vitro cytotoxicity assays against Leishmania (L.) amazonensis and Leishmania (L.) infantum promastigotes have shown that complexes [RuCl(dic)(η6-p-cymene)] (1) and [RuCl(nap)(η6-p-cymene)] (3) were active against both Leishmania species. Complex [RuCl(ibu)(η6-p-cymene)] (2) has exhibited no activity. The IC50 values for the two active complexes were respectively 7.42 and 23.55 μM, for L. (L.) amazonensis, and 8.57 and 42.25 μM, for L. (L.) infantum. Based on the toxicological results and computational analysis, we proposed a correlation between the complexes and their activity. Our results suggest both complexation to ruthenium(II) and ligands structure are key elements to leishmanicidal activity.
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Acknowledgements
We thank the Brazilian Agencies of Research: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and Grupo de Materiais Inorganicos do Triângulo (GMIT), research group funded by FAPEMIG. The authors are also thankful to the Multiuser Laboratory of the Instituto de Química at Universidade Federal de Uberlândia for providing the equipment and technical support for elemental analysis and 1H-NMR.
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Miranda, V.M., Costa, M.S., Guilardi, S. et al. In vitro leishmanicidal activity and theoretical insights into biological action of ruthenium(II) organometallic complexes containing anti-inflammatories. Biometals 31, 1003–1017 (2018). https://doi.org/10.1007/s10534-018-0145-z
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DOI: https://doi.org/10.1007/s10534-018-0145-z