| Literature DB >> 27586460 |
Ligia F Martins1, Juliana T Mesquita1, Erika G Pinto1,2, Thais A Costa-Silva1, Samanta E T Borborema1, Andres J Galisteo Junior2, Bruno J Neves3, Carolina H Andrade3, Zainab Al Shuhaib4, Elliot L Bennett4, Gregory P Black4, Philip M Harper4, Daniel M Evans4, Hisham S Fituri4, John P Leyland4, Claire Martin4, Terence D Roberts4, Andrew J Thornhill4, Stephen A Vale4, Andrew Howard-Jones4, Dafydd A Thomas4, Harri L Williams4, Larry E Overman5, Roberto G S Berlinck6, Patrick J Murphy4, Andre G Tempone1.
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.Entities:
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Year: 2016 PMID： 27586460 DOI： 10.1021/acs.jnatprod.6b00256
Source DB: PubMed Journal: J Nat Prod ISSN： 0163-3864 Impact factor: 4.050