Anti-parasitic Guanidine and Pyrimidine Alkaloids from the Marine Sponge Monanchora arbuscula.
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).
†Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970 São Carlos, SP, Brazil.
Mario F C
MF
Santos
‡School of Chemistry, Bangor University, Bangor, Gwynedd LL57 2UW, U.K.
Philip M
PM
Harper
David E
DE
Williams
⊥Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, Cerqueira Cesar, CEP 01246-000 São Paulo, SP, Brazil.
Juliana T
JT
Mesquita
⊥Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, Cerqueira Cesar, CEP 01246-000 São Paulo, SP, Brazil.|∥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.
Érika G
ÉG
Pinto
⊥Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, Cerqueira Cesar, CEP 01246-000 São Paulo, SP, Brazil.
Thais A
TA
da Costa-Silva
#Museu Nacional, Universidade Federal do Rio de Janeiro, Quinta da Boa Vista, s/n, CEP 20940-040 Rio de Janeiro, RJ, Brazil.
Eduardo
E
Hajdu
∇Departamento de Química, Universidade Federal de São Carlos, Rod. Washington Luiz, km 235 - SP-310, CEP 13565-905, São Carlos, SP, Brazil.
Antonio G
AG
Ferreira
⊗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.
Raquel A
RA
Santos
‡School of Chemistry, Bangor University, Bangor, Gwynedd LL57 2UW, U.K.
Patrick J
PJ
Murphy
Raymond J
RJ
Andersen
⊥Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, Cerqueira Cesar, CEP 01246-000 São Paulo, SP, Brazil.|∥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.
Andre G
AG
Tempone
†Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970 São Carlos, SP, Brazil.
Roberto G S
RG
Berlinck
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D001938:Brazil; D006146:Guanidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018314:Leishmania infantum / Q000187:drug effects; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D021261:Parasitic Sensitivity Tests; D011161:Porifera / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
D000470:Alkaloids; D006146:Guanidines; D011743:Pyrimidines; C000599863:arbusculidine A; C000599864:batzellamide A; C000599862:monalidine A