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

• Published in: Journal of natural products (Washington, D.C.) Vol. 78; no. 5; pp. 1101 - 1112
• Main Authors: Santos, Mario F. C, Harper, Philip M, Williams, David E, Mesquita, Juliana T, Pinto, Érika G, da Costa-Silva, Thais A, Hajdu, Eduardo, Ferreira, Antonio G, Santos, Raquel A, Murphy, Patrick J, Andersen, Raymond J, Tempone, Andre G, Berlinck, Roberto G. S
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 22-05-2015
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Brazil; Guanidines - chemistry; Guanidines - isolation & purification; Guanidines - pharmacology; Leishmania infantum - drug effects; Marine Biology; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Parasitic Sensitivity Tests; Porifera - chemistry; Pyrimidines - chemistry; Pyrimidines - isolation & purification; Pyrimidines - pharmacology; Trypanosoma cruzi - drug effects; Brazil
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00070

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).