title: Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes.
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.
authors: Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.
authors: Ligia F
authors: LF
authors: Martins
authors: Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.
authors: Juliana T
authors: JT
authors: Mesquita
authors: Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.|Instituto de Medicina Tropical, Universidade de São Paulo , Avenida Dr. Enéas de Carvalho Aguiar, 470, 05403-000 São Paulo, SP, Brazil.
authors: Erika G
authors: EG
authors: Pinto
authors: Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.
authors: Thais A
authors: TA
authors: Costa-Silva
authors: Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.
authors: Samanta E T
authors: SE
authors: Borborema
authors: Instituto de Medicina Tropical, Universidade de São Paulo , Avenida Dr. Enéas de Carvalho Aguiar, 470, 05403-000 São Paulo, SP, Brazil.
authors: Andres J
authors: AJ
authors: Galisteo Junior
authors: LabMol, Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás , Goiânia, Brazil.
authors: Bruno J
authors: BJ
authors: Neves
authors: LabMol, Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás , Goiânia, Brazil.
authors: Carolina H
authors: CH
authors: Andrade
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Zainab Al
authors: ZA
authors: Shuhaib
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Elliot L
authors: EL
authors: Bennett
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Gregory P
authors: GP
authors: Black
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Philip M
authors: PM
authors: Harper
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Daniel M
authors: DM
authors: Evans
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Hisham S
authors: HS
authors: Fituri
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: John P
authors: JP
authors: Leyland
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Claire
authors: C
authors: Martin
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Terence D
authors: TD
authors: Roberts
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Andrew J
authors: AJ
authors: Thornhill
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Stephen A
authors: SA
authors: Vale
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Andrew
authors: A
authors: Howard-Jones
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Dafydd A
authors: DA
authors: Thomas
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Harri L
authors: HL
authors: Williams
authors: University of California, Irvine , 4042A Frederick Reines Hall, Irvine, California 92697, United States.
authors: Larry E
authors: LE
authors: Overman
authors: Instituto de Química de São Carlos, Universidade de São Paulo , CP 780, CEP 13560-970, São Carlos, SP, Brazil.
authors: Roberto G S
authors: RG
authors: Berlinck
authors: School of Chemistry, Bangor University , Bangor, Gwynedd, Wales, U.K. LL57 2UW.
authors: Patrick J
authors: PJ
authors: Murphy
authors: Centre for Parasitology and Mycology, Instituto Adolfo Lutz , Avenida Dr. Arnaldo, 351, 8° andar, 01246-000 São Paulo, SP, Brazil.
authors: Andre G
authors: AG
authors: Tempone
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018314:Leishmania infantum / Q000187:drug effects*; D008386:Marine Biology; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D006146:Guanidines; D009569:Nitric Oxide