Treatment using vanillin-derived synthetic molecules incorporated into polymeric micelles is effective against infection caused by Leishmania amazonensis species

Isabela A G Pereira; Camila S Freitas; Raquel S B Câmara; Marcelo M Jesus; Daniela P Lage; Grasiele S V Tavares; Tauane G Soyer; Fernanda F Ramos; Nícia P Soares; Samira S Santiago; Vívian T Martins; Danniele L Vale; Breno L Pimenta; Fernanda Ludolf; Fabrício M Oliveira; Mariana C Duarte; Miguel A Chávez-Fumagalli; Adilson V Costa; Denise U Gonçalves; Bruno M Roatt; Róbson R Teixeira; Eduardo A F Coelho

doi:10.1016/j.exppara.2024.108743

Treatment using vanillin-derived synthetic molecules incorporated into polymeric micelles is effective against infection caused by Leishmania amazonensis species

Exp Parasitol. 2024 Mar 19:260:108743. doi: 10.1016/j.exppara.2024.108743. Online ahead of print.

Authors

Isabela A G Pereira¹, Camila S Freitas¹, Raquel S B Câmara¹, Marcelo M Jesus¹, Daniela P Lage¹, Grasiele S V Tavares¹, Tauane G Soyer¹, Fernanda F Ramos¹, Nícia P Soares², Samira S Santiago³, Vívian T Martins¹, Danniele L Vale¹, Breno L Pimenta¹, Fernanda Ludolf⁴, Fabrício M Oliveira⁵, Mariana C Duarte⁶, Miguel A Chávez-Fumagalli⁷, Adilson V Costa⁸, Denise U Gonçalves¹, Bruno M Roatt², Róbson R Teixeira³, Eduardo A F Coelho⁹

Affiliations

¹ Programa de Pós-Graduação Em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Santa Efigênia, 30130-100, Belo Horizonte, Minas Gerais, Brazil.
² Laboratório de Imunopatologia, Núcleo de Pesquisas Em Ciências Biológicas, Departamento de Ciências Biológicas, Insituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
³ Grupo de Síntese e Pesquisa de Compostos Bioativos, Departamento de Química, Universidade Federal de Viçosa, Avenida PH Rolfs, S/N, 36570-900, Viçosa, Minas Gerais, Brazil.
⁴ Programa de Pós-Graduação Em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Santa Efigênia, 30130-100, Belo Horizonte, Minas Gerais, Brazil; Programa de Pós-Graduação Em Ciências da Saúde, Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, 30130-110, Minas Gerais, Brazil.
⁵ Instituto Federal de Educação de Minas Gerais, Rua Afonso Sardinha, 90, Bairro Pioneiros, 36420-000, Ouro Branco, Minas Gerais, Brazil.
⁶ Programa de Pós-Graduação Em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Santa Efigênia, 30130-100, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
⁷ Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Católica de Santa María, Urb. San José S/N, Umacollo, Arequipa, Peru.
⁸ Departamento de Química e Física, Universidade Federal Do Espírito Santo, Alto Universitário, S/n, Guararema, 29500-000, Alegre, Espírito Santo, Brazil.
⁹ Programa de Pós-Graduação Em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Santa Efigênia, 30130-100, Belo Horizonte, Minas Gerais, Brazil; Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil. Electronic address: eduardoferrazcoelho@yahoo.com.br.

PMID: 38513973
DOI: 10.1016/j.exppara.2024.108743

Abstract

Treatment against leishmaniasis presents problems, mainly due to the toxicity of the drugs, high cost, and the emergence of resistant strains. A previous study showed that two vanillin-derived synthetic molecules, 3s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], presented antileishmanial activity against Leishmania infantum, L. amazonensis, and L. braziliensis species. In the present work, 3s and 3t were evaluated to treat L. amazonensis-infected mice. Molecules were used pure or incorporated into Poloxamer 407-based micelles. In addition, amphotericin B (AmpB) and its liposomal formulation, Ambisome®, were used as control. Animals received the treatment and, one and 30 days after, they were euthanized to evaluate immunological, parasitological, and biochemical parameters. Results showed that the micellar compositions (3s/Mic and 3t/Mic) induced significant reductions in the lesion mean diameter and parasite load in the infected tissue and distinct organs, as well as a specific and significant antileishmanial Th1-type immune response, which was based on significantly higher levels of IFN-γ, IL-12, nitrite, and IgG2a isotype antibodies. Drug controls showed also antileishmanial action; although 3s/Mic and 3t/Mic have presented better and more significant parasitological and immunological data, which were based on significantly higher IFN-γ production and lower parasite burden in treated animals. In addition, significantly lower levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in mice treated with 3s/Mic and 3t/Mic, when compared to the others. In conclusion, results suggest that 3s/Mic and 3t/Mic could be considered as therapeutic candidates to treat against L. amazonensis infection.

Keywords: Amphotericin B; Leishmania amazonensis; Polymeric micelles; Tegumentary leishmaniasis; Treatment; Vanillin.