Biotransformation of a tetrahydrofuran lignan by the endophytic fungus Phomopsis Sp.

Abstract

A biotransformação da lignana tetraidrofurânica, (-)-grandisina, pelo fungo endofítico Phomopsis sp, obtido de Viguiera arenaria, conduziu à formação de um novo metabólito caracterizado como 3,4-dimetil-2-(4'-hidróxi-3',5'-dimetóxifenil)-5-metóxi-tetraidrofurano. O metabólito foi analisado contra o parasita Trypanosoma cruzi, o agente causador da doença de Chagas, e mostrou uma atividade tripanocida (IC 50 9,8 µmol L -1 ) similar ao precursor natural (IC 50 3,7 µmol L -1 ).The biotrasformation of the tetrahydrofuran lignan, (-)-grandisin, by the endophitic fungus Phomopsis sp, obtained from Viguiera arenaria, led to the formation of a new compound determined as 3,4-dimethyl-2-(4'-hydroxy-3',5'-dimethoxyphenyl)-5-methoxy-tetrahydrofuran. The metabolite was evaluated against the parasite Trypanosoma cruzi, the causative agent of Chagas's disease, and showed a trypanocidal activity (IC 50 9.8 µmol L -1 ) similar to the natural precursor (IC 50 3.7 µmol L -1 ).Keywords: biotransformation, 2,5-diaryltetrahydrofuran, endophytic fungus, (-)-grandisin, trypanocidal activity IntroductionThe lignan family is a large group of natural products with noteworthy therapeutic activity as illustrated by podophyllotoxin derivatives (e. g. etoposide) with antitumoral activity. 1 In particular, the optically active tetrahydrofuran lignans display a wide range of pharmacological activities, including anti-parasite, 2-4 antibacterial, 5 antifungal, 6 antitumoral, 7 anti-inflammatory 8,9 and platelet-activating factor (PAF) inhibition. [10][11][12] Several non-symmetrical 2,5-diaryltetrahydrofuran lignans, shown in Table 1, have been isolated from Piper species (Piperaceae) containing either piperonyl, veratryl or 3,4,5-trimethoxyphenyl substituent at 2 and 5 positions and methyl groups at 3 and 4 positions attached to the tetrahydrofuran ring, as illustrated by (+)-calopiptin P. futokadsura, P. hancei, P. puberculum, P.wallichii), (-)-galbelgin (5, P. attenuatum, P. futokadsura, P. thomsoni, P. wightii), (+)-grandisin (6, P. polysyphorum), (+)-machilin G (7, P. schmidtii, P. wightii), (+)-veraguensin (8, P. cuneifolium, P. futokadsura, P. puberculum) and (-)-zuonin A (9, P. schmidtii). 13 Other bis-tetrahydrofuran lignans have also been described from Achillea lingulata (Asteraceae). 14 In previous reports, Martins et al. 3 described the isolation of (-)-grandisin (6) from Piper solmsianum and Lopes and co-workers 4,15 from Virola surinamensis (Rol.) Warb, which belong to Piperaceae and Myristicaceae, respectively. The tetrahydrofuran lignan (-)-grandisin (6) showed a potent trypanocidal activity against the trypomastigote form of Trypanosoma cruzi, responsible for Chagas´s disease in Latin America, at 5 µg mL -1 leading to a total parasite lysis after 24 h, without hematiae damage. 4 Furthermore, veraguensin (8) also isolated from Virola surinamensis 4 preserved this anti-parasite pattern along with a potent platelet-activating factor (PAF) inhibitory activity that may be involved in the mechanisms of the parasite growing and diffe...

Endophytic Fungi of Tropical Forests: A Promising Source of Bioactive Prototype Molecules for the Treatment of Neglected Diseases

“…7, 11). The metabolite had trypanocidal activity (IC 50 9.8 μmol/mL) similar to the natural precursor (IC 50 3.7 μmol/mL) (Verza et al, 2009). Fig.…”

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

“…The residue purified by column chromatography on silica gel using hexane/ethyl acetate 8:2 as eluent. General procedure for the preparation of triazole derivatives (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) To a solution of terminal acetylenes 25a-d (2 mmol, 1.0 equiv) and azides 27a-d (2 mmol, 1.0 equiv) in dichloromethane (2 mL) and water (2 mL), were added CuSO 4 .5H 2 O pentahydrate (0.128 mmol, 0.064 equiv) and sodium ascorbate (0.352 mmol, 0.176 equiv). The reaction mixture was stirred for 24 h. Then was added a saturated solution of NH 4 Cl (30 mL) and the product was extracted with dichloromethane (3 × 20 mL).…”

“…10,12,13 Among natural products, our research group has focused on the tetrahydrofuran neolignans, a class that exhibits a great number of biological activities including antibacterial, antifungal, antitumor, and anti-inflammatory. [14][15][16][17][18][19][20][21][22][23] The neolignans veraguensin 1, grandisin 2, and machilin G 3 ( Figure 1) have shown antitrypanosomal and antileishmanial activities. [14][15][16][17][18][19][20][21][22][23] Studies on the antitrypanosomal activity of compounds 1-3 found maximum inhibitory concentration (IC 50 ) values of 2.3, 3.7 and 2.2 µM, respectively.…”

Immobilization of Lipases Produced by the Endophytic Fungus Cercospora kikuchii on Chitosan Microparticles

“…Endophytic fungi have also drawn attention as potential producers of many products, including industrially interesting enzymes. Endophytic fungi exhibit a complex web of interactions with the host plants and have been extensively studied over the last several years as prolific sources of new bioactive natural products, including new enzymes with interesting properties for industrial application (Verza et al 2009;Borges et al 2009;Fernandes et al 2009). However, very few endophytic fungi have been reported as producers of lipase.…”