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Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis

Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis
Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis
Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4`-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L. amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L. infantum and L. amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L. infantum and L. amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L. infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response was developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.
0141-9838
Pereira, Isabela A G
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Mendoca, Debora V.C.
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Tavares, Grasiele S.V.
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Lage, Daniela P
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Fonseca Ramos, Fernanda
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Oliveira-da-Silva, Joao A
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Antinarelli, Luciana M.R.
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Sanchez Machado, Amanda
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Carvalho, Livia M.
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Carvalho, Ana Maria R S
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Salustiano, Iorrana V
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Reis, Thiago A.R.
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Bandeira, Raquel S
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Silva, Alessandra M
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Martins, Vivian T
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Chavez-Fumagalli, Miguel A
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Humbert, Maria V
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Roatt, Bruno M.
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Duarte, Mariana C
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Menezes-Souza, Daniel
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Coimbra, Elaine S
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Leite, Joao Paulo V
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Ferraz Coelho, Eduardo Antonio
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Goncalves, Denise U
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Pereira, Isabela A G
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Mendoca, Debora V.C.
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Tavares, Grasiele S.V.
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Lage, Daniela P
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Fonseca Ramos, Fernanda
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Oliveira-da-Silva, Joao A
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Antinarelli, Luciana M.R.
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Sanchez Machado, Amanda
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Carvalho, Livia M.
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Carvalho, Ana Maria R S
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Salustiano, Iorrana V
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Reis, Thiago A.R.
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Bandeira, Raquel S
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Silva, Alessandra M
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Martins, Vivian T
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Chavez-Fumagalli, Miguel A
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Humbert, Maria V
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Roatt, Bruno M.
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Duarte, Mariana C
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Menezes-Souza, Daniel
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Coimbra, Elaine S
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Leite, Joao Paulo V
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Ferraz Coelho, Eduardo Antonio
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Goncalves, Denise U
8f95969b-3309-4105-b725-40f100136b1d

Pereira, Isabela A G, Mendoca, Debora V.C., Tavares, Grasiele S.V., Lage, Daniela P, Fonseca Ramos, Fernanda, Oliveira-da-Silva, Joao A, Antinarelli, Luciana M.R., Sanchez Machado, Amanda, Carvalho, Livia M., Carvalho, Ana Maria R S, Salustiano, Iorrana V, Reis, Thiago A.R., Bandeira, Raquel S, Silva, Alessandra M, Martins, Vivian T, Chavez-Fumagalli, Miguel A, Humbert, Maria V, Roatt, Bruno M., Duarte, Mariana C, Menezes-Souza, Daniel, Coimbra, Elaine S, Leite, Joao Paulo V, Ferraz Coelho, Eduardo Antonio and Goncalves, Denise U (2020) Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis. Parasite Immunology, 42 (12), [e12784]. (doi:10.1111/pim.12784).

Record type: Article

Abstract

Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4`-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L. amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L. infantum and L. amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L. infantum and L. amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L. infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response was developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.

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Accepted/In Press date: 3 August 2020
e-pub ahead of print date: 30 August 2020
Published date: December 2020

Identifiers

Local EPrints ID: 447471
URI: http://eprints.soton.ac.uk/id/eprint/447471
ISSN: 0141-9838
PURE UUID: 8b484eef-8bf3-453c-bdbc-62fbaef9fae9
ORCID for Maria V Humbert: ORCID iD orcid.org/0000-0002-5728-6981

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Date deposited: 12 Mar 2021 17:30
Last modified: 07 Oct 2021 01:46

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Contributors

Author: Isabela A G Pereira
Author: Debora V.C. Mendoca
Author: Grasiele S.V. Tavares
Author: Daniela P Lage
Author: Fernanda Fonseca Ramos
Author: Joao A Oliveira-da-Silva
Author: Luciana M.R. Antinarelli
Author: Amanda Sanchez Machado
Author: Livia M. Carvalho
Author: Ana Maria R S Carvalho
Author: Iorrana V Salustiano
Author: Thiago A.R. Reis
Author: Raquel S Bandeira
Author: Alessandra M Silva
Author: Vivian T Martins
Author: Miguel A Chavez-Fumagalli
Author: Maria V Humbert ORCID iD
Author: Bruno M. Roatt
Author: Mariana C Duarte
Author: Daniel Menezes-Souza
Author: Elaine S Coimbra
Author: Joao Paulo V Leite
Author: Eduardo Antonio Ferraz Coelho
Author: Denise U Goncalves

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