Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

Ligia F. Martins; Juliana T. Mesquita; Erika G. Pinto; Thais A. Costa-Silva; Samantha E. T. Borborema; Andres J.  Galisteo Junior; Bruno J.  Neves; Carolina H.  Andrade; Elliot Bennett; Gregory Black; Philip Harper; Daniel Evans; Hisham Fituri; John P. Leyland; Claire Martin; Terence Roberts; Andrew J. Thornhill; Steven Vale; Andrew Howard-Jones; Dafydd Thomas; Harri L. Williams; Larry Overman; Roberto  Berlinck; Patrick Murphy; Andre  Tempone

doi:10.1021/acs.jnatprod.6b00256

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

Ligia F. Martins, Juliana T. Mesquita, Erika G. Pinto, Thais A. Costa-Silva, Samantha E. T. Borborema, Andres J. Galisteo Junior, Bruno J. Neves, Carolina H. Andrade, Elliot Bennett, Gregory Black, Philip Harper, Daniel Evans, Hisham Fituri, John P. Leyland, Claire Martin, Terence Roberts, Andrew J. Thornhill, Steven Vale, Andrew Howard-Jones, Dafydd ThomasHarri L. Williams, Larry Overman, Roberto Berlinck, Patrick Murphy, Andre Tempone

Research output: Contribution to journal › Article › peer-review

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Abstract

ABSTRACT: Synthetic analogues of marine sponge guanidine
alkaloids showed in vitro antiparasitic activity against
Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines
10 and 11 presented the highest selectivity index when tested
against Leishmania. The antiparasitic activity of 10 and 11 was
investigated in host cells and in parasites. Both compounds
induced depolarization of mitochondrial membrane potential,
upregulation of reactive oxygen species levels, and increased
plasma membrane permeability in Leishmania parasites.
Immunomodulatory assays suggested an NO-independent
effect of guanidines 10 and 11 on macrophages. The same
compounds also promoted anti-inflammatory activity in L. (L.)
infantum-infected macrophages cocultived with splenocytes,
reducing the production of cytokines MCP-1 and IFN-γ.
Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a hostindependent
mechanism.

Original language	English
Pages (from-to)	2202-2210
Number of pages	9
Journal	Journal of natural products
Volume	79
Issue number	9
Early online date	2 Sept 2016
DOIs	https://doi.org/10.1021/acs.jnatprod.6b00256
Publication status	Published - 16 Sept 2016

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Martins, L. F., Mesquita, J. T., Pinto, E. G., Costa-Silva, T. A., Borborema, S. E. T., Galisteo Junior, A. J., Neves, B. J., Andrade, C. H., Bennett, E., Black, G., Harper, P., Evans, D., Fituri, H., Leyland, J. P., Martin, C., Roberts, T., Thornhill, A. J., Vale, S., Howard-Jones, A., ... Tempone, A. (2016). Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes. Journal of natural products, 79(9), 2202-2210. https://doi.org/10.1021/acs.jnatprod.6b00256

@article{3eeee0c218ce4b6c80d5f16bdc339ff9,

title = "Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes",

abstract = "ABSTRACT: Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a hostindependent mechanism.",

author = "Martins, \{Ligia F.\} and Mesquita, \{Juliana T.\} and Pinto, \{Erika G.\} and Costa-Silva, \{Thais A.\} and Borborema, \{Samantha E. T.\} and \{Galisteo Junior\}, \{Andres J.\} and Neves, \{Bruno J.\} and Andrade, \{Carolina H.\} and Elliot Bennett and Gregory Black and Philip Harper and Daniel Evans and Hisham Fituri and Leyland, \{John P.\} and Claire Martin and Terence Roberts and Thornhill, \{Andrew J.\} and Steven Vale and Andrew Howard-Jones and Dafydd Thomas and Williams, \{Harri L.\} and Larry Overman and Roberto Berlinck and Patrick Murphy and Andre Tempone",

year = "2016",

month = sep,

day = "16",

doi = "10.1021/acs.jnatprod.6b00256",

language = "English",

volume = "79",

pages = "2202--2210",

journal = "Journal of natural products",

issn = "0163-3864",

publisher = "American Chemical Society",

number = "9",

}

Martins, LF, Mesquita, JT, Pinto, EG, Costa-Silva, TA, Borborema, SET, Galisteo Junior, AJ, Neves, BJ, Andrade, CH, Bennett, E, Black, G, Harper, P, Evans, D, Fituri, H, Leyland, JP, Martin, C, Roberts, T, Thornhill, AJ, Vale, S, Howard-Jones, A, Thomas, D, Williams, HL, Overman, L, Berlinck, R, Murphy, P & Tempone, A 2016, 'Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes', Journal of natural products, vol. 79, no. 9, pp. 2202-2210. https://doi.org/10.1021/acs.jnatprod.6b00256

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes. / Martins, Ligia F.; Mesquita, Juliana T.; Pinto, Erika G. et al.
In: Journal of natural products, Vol. 79, No. 9, 16.09.2016, p. 2202-2210.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

AU - Martins, Ligia F.

AU - Mesquita, Juliana T.

AU - Pinto, Erika G.

AU - Costa-Silva, Thais A.

AU - Borborema, Samantha E. T.

AU - Galisteo Junior, Andres J.

AU - Neves, Bruno J.

AU - Andrade, Carolina H.

AU - Bennett, Elliot

AU - Black, Gregory

AU - Harper, Philip

AU - Evans, Daniel

AU - Fituri, Hisham

AU - Leyland, John P.

AU - Martin, Claire

AU - Roberts, Terence

AU - Thornhill, Andrew J.

AU - Vale, Steven

AU - Howard-Jones, Andrew

AU - Thomas, Dafydd

AU - Williams, Harri L.

AU - Overman, Larry

AU - Berlinck, Roberto

AU - Murphy, Patrick

AU - Tempone, Andre

PY - 2016/9/16

Y1 - 2016/9/16

N2 - ABSTRACT: Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a hostindependent mechanism.

AB - ABSTRACT: Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a hostindependent mechanism.

U2 - 10.1021/acs.jnatprod.6b00256

DO - 10.1021/acs.jnatprod.6b00256

M3 - Article

SN - 0163-3864

VL - 79

SP - 2202

EP - 2210

JO - Journal of natural products

JF - Journal of natural products

IS - 9

ER -

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

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