RESUMO
Marine sponges from the Plakinidae family are well known for hosting cytotoxic secondary metabolites and the Brazilian Atlantic coast and its oceanic islands have been considered as a hotspot for the discovery of new Plakinidae species. Herein, we report the chemical profile among cytotoxic extracts obtained from four species of Plakinidae, collected in Fernando de Noronha Archipelago (PE, Northeastern Brazil). Crude organic extracts of Plakinastrella microspiculifera, Plakortis angulospiculatus, Plakortis insularis, and Plakortis petrupaulensis showed strong antiproliferative effects against two different cancer cell lines (HCT-116: 86.7-100%; MCF-7: 74.9-89.5%) at 50 µg/mL, by the MTT assay. However, at a lower concentration (5 µg/mL), high variability in inhibition of cell growth was observed (HCT-116: 17.3-68.7%; MCF-7: 0.00-55.5%), even within two samples of Plakortis insularis which were collected in the west and east sides of the Archipelago. To discriminate the chemical profile, the samples were investigated by UHPLC-HRMS under positive ionization mode. The produced data was uploaded to the Global Natural Products Social Molecular Networking and organized based on spectral similarities for purposes of comparison and annotation. Compounds such as dipeptides, nucleosides and derivatives, polyketides, and thiazine alkaloids were annotated and metabolomic differences were perceived among the species. To the best of our knowledge, this is the first assessment for cytotoxic activity and chemical profiling for Plakinastrella microspiculifera, Plakortis insularis and Plakortis petrupaulensis, revealing other biotechnologically relevant members of the Plakinidae family.
Assuntos
Metaboloma , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Brasil , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Humanos , Ilhas , Células MCF-7 , Metabolômica , Neoplasias/tratamento farmacológico , Plakortis/química , Plakortis/metabolismo , Poríferos/metabolismoRESUMO
Fractionation of the bioactive CHCl3-MeOH (1:1) extracts obtained from two collections of the sponge consortium Plakortis symbiotica-Xestospongia deweerdtae from Puerto Rico provided two new plakinidone analogues, designated as plakinidone B (2) and plakinidone C (3), as well as the known plakinidone (1), plakortolide F (4), and smenothiazole A (5). The structures of 1-5 were characterized on the basis of 1D and 2D NMR spectroscopic, IR, UV, and HRMS analysis. The absolute configurations of plakinidones 2 and 3 were established through chemical correlation methods, VCD/ECD experiments, and spectroscopic data comparisons. When assayed in vitro against Mycobacterium tuberculosis H37Rv, none of the plakinidones 1-3 displayed significant activity, whereas smenothiazole A (5) was the most active compound, exhibiting an MIC value of 4.1 µg/mL. Synthesis and subsequent biological screening of 8, a dechlorinated version of smenothiazole A, revealed that the chlorine atom in 5 is indispensable for anti-TB activity.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/química , Peróxidos/farmacologia , Plakortis/química , Tiazóis/síntese química , Tiazóis/farmacologia , Valina/análogos & derivados , Xestospongia/química , Animais , Antituberculosos/síntese química , Antituberculosos/química , Produtos Biológicos , Dioxinas/síntese química , Dioxinas/química , Dioxinas/farmacologia , Lactonas/síntese química , Lactonas/química , Lactonas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Mycobacterium tuberculosis/metabolismo , Peróxidos/síntese química , Peróxidos/química , Porto Rico , Tiazóis/química , Valina/síntese química , Valina/química , Valina/farmacologiaRESUMO
Plakortinic acids A (2) and B (3), two polyketide endoperoxides with a bicyclo[4.2.0]octene unit, were isolated as minor constituents from the sponge-sponge symbiotic association Plakortis halichondrioides-Xestospongia deweerdtae, along with known epiplakinic acid F (1). The structures of the mixture of two inseparable compounds were determined by spectroscopic analysis. Screening for cytotoxic activity of the mixture against two human tumor cell lines revealed that these compounds are very active at sub-micromolar concentration.
Assuntos
Peróxidos/química , Plakortis/química , Policetídeos/química , Xestospongia/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Peróxidos/isolamento & purificação , Peróxidos/farmacologia , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , EstereoisomerismoRESUMO
Two new five-membered-ring polyketide endoperoxides, epiplakinic acid F methyl ester (1) and epiplakinidioic acid (3), and a peroxide-lactone, plakortolide J (2), were isolated from the Puerto Rican sponge Plakortis halichondrioides, along with two previously reported cyclic peroxides, 4 and 5. The structures of the new metabolites were determined by spectroscopic and chemical analyses. The absolute stereostructures of 1, 2, and 5 were determined by degradation reactions followed by application of Kishi's method for the assignment of absolute configuration of alcohols. Biological screening of cycloperoxides 1-5 and semisynthetic analogues 7-12 for cytotoxic activity against various human tumor cell lines revealed that compounds 3, 4, and 11 are very active. Upon assaying for antimalarial and antitubercular activity, some of the compounds tested showed strong activity against the pathogenic microbes Plasmodium falciparum and Mycobacterium tuberculosis.
Assuntos
Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antituberculosos/isolamento & purificação , Antituberculosos/farmacologia , Compostos Heterocíclicos com 2 Anéis/isolamento & purificação , Compostos Heterocíclicos com 2 Anéis/farmacologia , Peróxidos/isolamento & purificação , Peróxidos/farmacologia , Plakortis/química , Animais , Antimaláricos/química , Antituberculosos/química , Compostos Heterocíclicos com 2 Anéis/química , Humanos , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Peróxidos/química , Plasmodium falciparum/efeitos dos fármacos , Porto RicoRESUMO
Investigation of the bioactive crude extract from the sponge Plakortis angulospiculatus from Brazil led to the isolation of plakortenone ( 1) as a new polyketide, along with five known polyketides ( 2- 6) previously isolated from other Plakortis sponges. The known polyketides were tested in antileishmanial, antitrypanosomal, antineuroinflammatory, and cytotoxicity assays. The results show that plakortide P ( 3) is a potent antiparasitic compound, against both Leishmania chagasi and Trypanosona cruzi, and exhibited antineuroinflammatory activity. The known polyketides 2- 6 were tested for cytotoxicity against four human cancer cell lines, but displayed only moderate cytotoxic activity.