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

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

  • J Nat Prod. 2016 Sep 23;79(9):2202-10. doi: 10.1021/acs.jnatprod.6b00256.
Ligia F Martins 1,  Juliana T Mesquita 1,  Erika G Pinto 1 2,  Thais A Costa-Silva 1,  Samanta E T Borborema 1,  Andres J Galisteo Junior 2,  Bruno J Neves 3,  Carolina H Andrade 3,  Zainab Al Shuhaib 4,  Elliot L Bennett 4,  Gregory P Black 4,  Philip M Harper 4,  Daniel M Evans 4,  Hisham S Fituri 4,  John P Leyland 4,  Claire Martin 4,  Terence D Roberts 4,  Andrew J Thornhill 4,  Stephen A Vale 4,  Andrew Howard-Jones 4,  Dafydd A Thomas 4,  Harri L Williams 4,  Larry E Overman 5,  Roberto G S Berlinck 6,  Patrick J Murphy 4,  Andre G Tempone 1
Affiliations

Affiliations

  • 1 Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.
  • 2 Instituto de Medicina Tropical, Universidade de São Paulo , Avenida Dr. Enéas de Carvalho Aguiar, 470, 05403-000 São Paulo, SP, Brazil.
  • 3 LabMol, Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás , Goiânia, Brazil.
  • 4 School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
  • 5 University of California, Irvine , 4042A Frederick Reines Hall, Irvine, California 92697, United States.
  • 6 Instituto de Química de São Carlos, Universidade de São Paulo , CP 780, CEP 13560-970, São Carlos, SP, Brazil.
PMID: 27586460 DOI: 10.1021/acs.jnatprod.6b00256
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 host-independent mechanism.

Figures