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Title: Isolation, Derivative Synthesis, and Structure−Activity Relationships of Antiparasitic Bromopyrrole Alkaloids from the Marine Sponge Tedania brasiliensis
Authors: L. Parra, Lizbeth L.
Bertonha, Ariane F.
M. Severo, Ivan R.
C. Aguiar, Anna C.
de Souza, Guilherme E.
Oliva, Glaucius
C. Guido, Rafael V.
Grazzia, Nathalia
Costa, Tábata R.
Miguel, Danilo C.
Gadelha, Fernanda R.
Ferreira, Antonio G.
Hajdu, Eduardo
Romo, Daniel
S. Berlinck, Roberto G.
Issue Date: 2018
Publisher: Journal of Natural Products
Abstract: The isolation and identification of a series of new pseudoceratidine (1) derivatives from the sponge Tedania brasiliensis enabled the evaluation of their anti-parasitic activity against Plasmodium falciparum, Leishmania (Leishmania) amazonensis, Leishmania (Leishmania) infantum and Trypanosoma cruzi, the causative agents of malaria, cutaneous leishmaniasis, visceral leishmaniasis and Chagas disease, respectively. The new 3-debromopseudoceratidine (4), 20-debromopseudoceratidine (5), 4-bromopseudoceratidine (6), 19-bromopseudoceratidine (7) and 4,19-dibromopseudoceratidine (8) are reported. New tedamides A – D (9 – 12), with an unprecedented 4-bromo-4-methoxy-5-oxo-4,5-dihydro-1H-pyrrole-2-carboxamide moiety, are also described. Compounds 4 and 5, 6 and 7, 9 and 10, and 11 and 12 have been isolated as pairs of inseparable structural isomers differing in their sites of bromination or oxidation. Tedamides 9+10 and 11+12 were obtained as optically active pairs, indicating an enzymatic formation rather than an artefactual origin. N12-Acetyl pseudoceratidine (2) and N12-formyl pseudoceratidine (3) were obtained by derivatization of pseudoceratidine (1). The anti-parasitic activity of pseudoceratidine (1) led us to synthesize 23 derivatives (16, 17, 20, 21, 23, 25, 27 – 29, 31, 33, 35, 38, 39, 42, 43, 46, 47, 50 and 51) with variations in the polyamine chain and aromatic moiety in sufficient amounts for biological evaluation in anti-parasitic assays. The measured anti-malarial activity of pseudoceratidine (1) and derivatives 4, 5, 16, 23, 25, 31 and 50 provided an initial SAR evaluation of these compounds as potential leads for anti-parasitics against Leishmania amastigotes and against Plasmodium falciparum. The results obtained indicate that pseudoceratidine represents a promising scaffold for the development of new anti-malarial drugs.
ISSN: 0163-3864
Appears in Collections:Producción Científica

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