Estudo químico e citotóxico de metabólitos secundários isolados de fungos endofíticos de Aroeira-do-Sertão (Myracrodruon urundeuva Fr. All.): Pseudofusicoccum stromaticum e Lasiodiplodia theobromae

Abstract

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.