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 Thomas

Harri L. Williams, Larry Overman, Roberto Berlinck, Patrick Murphy, Andre Tempone

Departamento de Ecologia, Universidade de São Paulo
Centre for Parasitology and Mycology, Instituto Adolfo Lutz,
Universidade Federal de Goiás
University of California, Irvine

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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.

Iaith wreiddiol	Saesneg
Tudalennau (o-i)	2202-2210
Nifer y tudalennau	9
Cyfnodolyn	Journal of natural products
Cyfrol	79
Rhif cyhoeddi	9
Dyddiad ar-lein cynnar	2 Medi 2016
Dynodwyr Gwrthrych Digidol (DOIs)	https://doi.org/10.1021/acs.jnatprod.6b00256
Statws	Cyhoeddwyd - 16 Medi 2016

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10.1021/acs.jnatprod.6b00256

2016 Analogues of Marine Guanidine AlkaloidsLlawysgrif awdur wedi’i dderbyn, 497 KB

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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, cyfrol. 79, rhif 9, tt. 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.
Yn: Journal of natural products, Cyfrol 79, Rhif 9, 16.09.2016, t. 2202-2210.

Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid

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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