Empresa Brasileira de Pesquisa AgropecuÃria / Banco do Nordeste do Brasil / Fungos endofÃticos tÃm sido apontados como uma fonte promissora de substÃncias biologicamente ativas, entre as quais compostos com potencial atividade anticÃncer. Neste contexto, o presente trabalho descreve o primeiro estudo de prospecÃÃo quÃmica e citotoxicidade de dois fungos endofÃticos isolados de Aroeira-do-sertÃo (Myracrodruon urundeuva Fr. All.): Pseudofusicoccum stromaticum (MUB58) e Lasiodiplodia theobromae (MUB65). Os extratos de acetato de etila MUB58 e MUB65 foram obtidos atravÃs de partiÃÃo lÃquido-liquido do caldo destas cepas fÃngicas, as quais foram cultivadas por 21 dias em extrato de BD e malte, respectivamente. Os extratos fÃngicos foram inicialmente analisados por cromatografia lÃquida de ultraeficiÃncia acoplada a espectrometria de massas de alta resoluÃÃo (CLUE-EM) e posteriormente submetidos a cromatografia em Sephadex LH-20, seguida de cromatografia lÃquida de alta eficiÃncia com detector de arranjo de diodo. AnÃlise de CLUE-EM permitiu caracterizar a presenÃa de sete metabÃlitos no extrato MUB-58: O-sulfato de colina, xantofusina, 7-hidroxi-1-isocromanona, Ãcido multicÃlico, djalonensona, 3-Ãcido carboxÃlico-8-metoxicarbonila-1-hidroxi-9-oxo-9H-xantona e ciclo-Phe-Leu-Val-Leu-Leu. AlÃm disso, foram isolados quatro metabÃlitos ciclo-L-Phe-D-Leu1-L-Leu2-L-Leu3-L-lle (FC1), 5-hidroxi-metilfurfural (FC2), rotenolona (FC3) e tefrosina (FC4). O composto FC1 à inÃdito na literatura, enquanto os compostos FC3 e FC4 estÃo sendo relatados pela primeira vez em fungos endofÃticos. Da mesma forma, a anÃlise CLUE-EM do extrato MUB-65 levou à caracterizaÃÃo quÃmica de oito compostos jà relatados na espÃcie L. theobromae: 4-hidroximeleina; meleina; (3R, 5R)- 5-hidroxila-de-O-metil-lasiodiplodina; (3R,5R)-hidroxilasiodiplodina; 2,4,6-trimetiloct-2-enoato,1,2,6,8a- tetrahidro-7-hidroxi-1-8a-dimetil-6-oxo-2-naftalenila; lasiodiplodina; lasiojasmonato A e lasiojasmonatos B ou C. Adicionalmente, dois metabÃlitos foram isolados: lasiodiplodina (LT1) e rel-11-12- (7âR*, 4âR*, 2âR*- tetrahidrofuro[1â,2â] piranil)- lasiodiplodina (LT2). O composto LT2 està sendo relatado pela primeira vez na literatura. As estruturas quÃmicas de todas as substÃncias isoladas foram elucidadas por espectrometrias de RessonÃncia MagnÃtica Nuclear de 1H e 13C, infravermelho e CLUE-EM. Os extratos e seus respectivos metabÃlitos isolados foram submetidos ao ensaio de citotoxicidade para avaliaÃÃo dos seus efeitos antiproliferativos frente a uma linhagem celular de cÃncer colorretal (HCT-116). O extrato de MUB58 apresentou significativa atividade (75%) correspondendo a um IC50 de 10,40 Âg.mL-1, enquanto o extrato de MUB65 foi inativo. Os metabÃlitos isolados LT1 (IC50 11,24 Âg.mL-1), FC3 (IC50 5,59 Âg.mL-1) e FC4 (IC50 0,51 Âg.mL-1) apresentaram atividades na faixa de 11,24 a 0,51 Âg.mL-1. / Endophytic fungi have been identified as a promising source of biologically active substances,including compounds with potential anticancer activity. In this context, this paper describes the first study of chemical prospecting and cytotoxicity two endophytic fungi isolated from Aroeira
-do-SertÃo(Myracrodruon urundeuva Fr.ll.):Pseudofusicoccum stromaticum (MUB-58) and Lasiodiplodia theobromae (MUB
- 65). The ethylacetate extracts MUB-58 and MUB-65 were obta
ined by liquid-liquid partition broth these fungal strains which were cultured for 21 days on BD and malt extract
, respectively. The fungal extracts were first analyzed by liquid chromatography of ultraefficiency coupled to spectrometry, high resolution mass (CLUE -MS) and
subsequently subjected to chromatography on Sephadex LH
- 20, followed by liquid chromatography of high efficiency with diode array detector. CLUE - MS analysis allowed to determine the prese nce of metabolites in seven MUB 58 extract: cholin - O - sulfate, xanthofusin, 7-hidroxy
-1-isochromanone, multico licacid, djalonensone, 8 -
methoxycarbonyl-1-hidroxy-9-oxo-9H-xanthene-3-carboxylix acidand cyclo-Phe-Leu-Val-Leu-Leu. In addition, were
isolated four metabolites:cycloL-Phe-D-Leu1-L-Leu2-L-Leu
3-L-Ile (FC1), 5-hidroxy-methilfurfural (FC2), rotenolone (FC3) and tephrosin (FC4).The compound
FC1 is unprecedented in the literature, while FC3 and
FC4 compounds are being reported for the first
time in en dophytic fungi. Likewise, a CLUE
- MS analysis the MUB - 65 extract led to
characterization of eight chemical compounds already reported in the species L. theobromae:4-hidroxymelein; Mellein;(3R,5R)-5-hidroxyl-de-O-methyl-lasiodiplodin;(3
R,5 R)- hydroxyla siodiplodin; 2,4,6-trimethyloct-2-enoic acid-1,2,6,8a-tetrahydro-7-hydroxy-1-8a-dimethyl-6-oxo-2-
naphtalenyl-ester;lasiodiplodin;lasiojasmonate A and lasiojasmonates B ou C. Additionally, two metabolites w
ere isolated: lasiodiplodin(LT1) and rel-11-12-(7'R* 4'R*, 2
'R*-tetrahydrofuro [1', 2'] pyranyl)-lasiodiplodin (LT2). The compound LT2 being first reported in the literature. The chemical structures of all isolated compounds were elucidated by spectrometries Nuclear Magnetic Resonance
1 H and 13C, IR and CLUE-MS. The extracts and
their isolated metabolites were subjected to the cytotoxicity assay to evaluate their
antiproliferative effects against a colorectal cancer cell line (HCT-116). The MUB-58 extract showed significant activity (75%) corresponding to an IC50of 10.40 μg.mL
-1, while the MUB65 extract was inactive. The LT1
isolated metabolites (IC5011.24 μg.mL-1), FC3(IC50
5.59 μg.mL-1) and FC4(IC500.51 μg.mL-1) showed activity in the range of 11.24 to 0.51 μg.mL-1.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:10877 |
| Date | 16 February 2016 |
| Creators | Aline Cavalcante Mesquita Sobreira |
| Contributors | OtÃlia DeusdÃnia Loiola Pessoa, Gilvandete Maria Pinheiro Santiago, Edy Sousa de Brito |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em QuÃmica, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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