Anti-parasitic Guanidine and Pyrimidine Alkaloids from the Marine Sponge Monanchora arbuscula

  • J Nat Prod. 2015 May 22;78(5):1101-12. doi: 10.1021/acs.jnatprod.5b00070.
Mario F C Santos  1 ,  Philip M Harper  2 ,  David E Williams ,  Juliana T Mesquita  3 ,  Érika G Pinto  3  4 ,  Thais A da Costa-Silva  3 ,  Eduardo Hajdu  5 ,  Antonio G Ferreira  6 ,  Raquel A Santos  7 ,  Patrick J Murphy  2 ,  Raymond J Andersen ,  Andre G Tempone  3  4 ,  Roberto G S Berlinck  1
Affiliations
  • 1. †Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970 São Carlos, SP, Brazil.
  • 2. ‡School of Chemistry, Bangor University, Bangor, Gwynedd LL57 2UW, U.K.
  • 3. ⊥Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, Cerqueira Cesar, CEP 01246-000 São Paulo, SP, Brazil.
  • 4. ∥Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470, CEP 05403-000 São Paulo, SP, Brazil.
  • 5. #Museu Nacional, Universidade Federal do Rio de Janeiro, Quinta da Boa Vista, s/n, CEP 20940-040 Rio de Janeiro, RJ, Brazil.
  • 6. ∇Departamento de Química, Universidade Federal de São Carlos, Rod. Washington Luiz, km 235 - SP-310, CEP 13565-905, São Carlos, SP, Brazil.
  • 7. ⊗Laboratório de Genética e Biologia Molecular, Programa de Pós-Graduação em Ciências, Universidade de Franca, Av. Dr. Armando Salles Oliveira, 201, CEP 14404 600 Franca, SP, Brazil.
PMID: 25924111 DOI: 10.1021/acs.jnatprod.5b00070
Abstract

HPLC-UV-ELSD-MS-guided fractionation of the Anti-parasitic extract obtained from the marine Sponge Monanchora arbuscula, collected off the southeastern coast of Brazil, led to the isolation of a series of guanidine and pyrimidine Alkaloids. The pyrimidines monalidine A (1) and arbusculidine A (7), as well as the guanidine Alkaloids batzellamide A (8) and hemibatzelladines 9-11, represent new minor constituents that were identified by analysis of spectroscopic data. The total synthesis of monalidine A confirmed its structure. Arbusculidine A (7), related to the ptilocaulin/mirabilin/netamine family of tricyclic guanidine Alkaloids, is the first in this family to possess a benzene ring. Batzellamide A (8) and hemibatzelladines 9-11 represent new carbon skeletons that are related to the batzelladines. Evaluation of the Anti-parasitic activity of the major known metabolites, batzelladines D (12), F (13), L (14), and nor-L (15), as well as of synthetic monalidine A (1), against Trypanosoma cruzi and Leishmania infantum is also reported, along with a detailed investigation of Parasite cell-death pathways promoted by batzelladine L (14) and norbatzelladine L (15).