Isolation, Derivative Synthesis, and Structure-Activity Relationships of Antiparasitic Bromopyrrole Alkaloids from the Marine Sponge Tedania brasiliensis

Author(s):Show less -

Parra, Lizbeth L. L. ^{[1, 2]} ; Bertonha, Ariane F. ^{[1, 3]} ; Severo, Ivan R. M. ^[1] ; Aguiar, Anna C. C. ^[4] ; de Souza, Guilherme E. ^[4] ; Oliva, Glaucius ^[4] ; Guido, Rafael V. C. ^[4] ; Grazzia, Nathalia ^{[5, 6]} ; Costa, Tabata R. ^{[5, 6]} ; Miguel, Danilo C. ^{[5, 6]} ; Gadelha, Fernanda R. ^{[5, 6]} ; Ferreira, Antonio G. ^[7] ; Hajdu, Eduardo ^[8] ; Romo, Daniel ^[3] ; Berlinck, Roberto G. S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, CP 780, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Santiago de Cali, Dept Quim, Calle 5 62-00, Santiago De Cali, Valle Del Cauca - Colombia

^[3] Baylor Univ, Dept Chem & Biochem, Waco, TX 76706 - USA

^[4] Inst Fis Sao Carlos, Ave Joao Dagnone, 1100, Jardim Santa Angelina, BR-13563120 Sao Carlos, SP - Brazil

^[5] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, BR-13083862 Campinas, SP - Brazil

^[6] Univ Estadual Campinas, Inst Biol, Dept Biol Anim, BR-13083862 Campinas, SP - Brazil

^[7] Univ Fed Sao Carlos, Dept Quim, Rod Washington Luiz, Km 235 SP 310, BR-13565905 Sao Carlos, SP - Brazil

^[8] Univ Fed Rio de Janeiro, Museu Nacl, Quinta Boa Vista S-N, BR-20940040 Rio De Janeiro, RJ - Brazil

• Document type: Journal article
• Source: Journal of Natural Products; v. 81, n. 1, p. 188-202, JAN 2018.
• Web of Science Citations: 3

Abstract

The isolation and identification of a series of new pseudoceratidine (1) derivatives from the sponge Tedania brasiliensis enabled the evaluation of their antiparasitic 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 artifactual origin. N-12-Acetylpseudoceratidine (2) and N-12-formylpseudoceratidine (3) were obtained by derivatization of pseudoceratidine (1). The antiparasitic 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 antiparasitic assays. The measured antimalarial 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 antiparasitics against Leishmania amastigotes and against P. falciparum. The results obtained indicate that pseudoceratidine represents a promising scaffold for the development of new antimalarial drugs. (AU)

• FAPESP's process: 15/24595-9 - Correlation between the biochemical parameters of Trypanosoma cruzi isolates from Chagas disease patients with different clinical forms of the disease and the pathogenesis of the disease
• Grantee: Fernanda Ramos Gadelha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/21129-4 - The role of fatty acid-binding proteins in the macrophage infection by Leishmania: a potential target for new drugs against leishmaniasis
• Grantee: Danilo Ciccone Miguel
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/50228-8 - Biodiversity components, and their metabolic characters, of Brazilian Islands: an integrated approach
• Grantee: Roberto Gomes de Souza Berlinck
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants