RESUMO
Epipolythiodioxopiperazines (ETPs) are a class of biologically active fungal secondary metabolites characterized by a bridged polysulfide piperazine ring. Regularly, the sulfide functionality is attached in the α-positions of the dioxopiperazine scaffold. However, ETPs possessing irregular sulfur bridges have rarely been explored. This review summarizes that 83 compounds of this subtype have been isolated and characterized since the discovery of gliovirin in 1982. Herein, particular emphasis is given to the isolation, chemistry, and biological activity of this subtype. For a better understanding, a relevant summary focusing on the source microorganisms and their taxonomy is provided and will help elucidate the fascinating chemistry and biology of these unusual ETPs.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Piperazinas/química , Piperazinas/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Eupenicillium/química , Fungos/química , Fungos/classificação , Gliocladium/química , Humanos , Células Jurkat , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
Seven undescribed polyketides javanicols A-E, 5-epi-citreoviridin and 5-epi-isocitreoviridin, together with five known compounds, were isolated from the endolichenic fungus Eupenicillium javanicum. The structures of these polyketides were determined by means of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR shift calculations. These compounds were evaluated for potential anti-inflammatory activity against LPS-activated RAW 264.7 cells. Javanicol E and (+)-terrein displayed moderate inhibitory effects on NO production, with IC50 values of 17.00 and 13.46⯵M, respectively.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Eupenicillium/química , Óxido Nítrico/antagonistas & inibidores , Policetídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Compostos Fitoquímicos , Policetídeos/química , Policetídeos/isolamento & purificação , Células RAW 264.7RESUMO
Three new indole diterpenes, penicilindoles A-C (1-3), were isolated from the mangrove-derived fungus Eupenicillium sp. HJ002. Their planar structures and absolute configurations were determined by interpretation of NMR spectroscopic data, HR-ESIMS, and X-ray diffraction analysis using Cu Kα radiation. The cytotoxic and antibacterial activities were evaluated in vitro; penicilindole A (1) showed cytotoxic activity against human A549 and HepG2 cell lines with IC50 values of 5.5 and 1.5 µM, respectively.
Assuntos
Citotoxinas/farmacologia , Diterpenos/farmacologia , Eupenicillium/química , Rhizophoraceae/microbiologia , Células A549 , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Citotoxinas/química , Diterpenos/química , Fungos , Células HeLa , Células Hep G2 , Humanos , Indóis/química , Indóis/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Penicillium/químicaRESUMO
An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD+-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-containing compounds, eupenicinicols C and D (3 and 4), along with two biosynthetically related known compounds, eujavanicol A (1) and eupenicinicol A (2). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECD calculations, as well as single-crystal X-ray diffraction. Compounds 3 and 4 exist in chemical equilibrium with two and three cis/trans isomers, respectively, as revealed by LC-MS analysis. Compound 4 was active against Staphylococcus aureus with an MIC of 0.1 µg/mL and demonstrated marked cytotoxicity against the human acute monocytic leukemia cell line (THP-1). We have shown that the HDAC inhibitor, nicotinamide, enhanced the production of compounds 3 and 4 by endophytic Eupenicillium sp. LG41, facilitating their isolation, structure elucidation, and evaluation of their biological activities.
Assuntos
Eupenicillium/química , Inibidores de Histona Desacetilases/farmacologia , Naftalenos/química , Xanthium/microbiologia , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Endófitos/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftalenos/isolamento & purificação , Naftalenos/farmacologia , Ressonância Magnética Nuclear Biomolecular , Penicillium/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Brefeldin A (BFA) is a macrolide lactone antibiotic, possessing antitumor, antiviral, antifungal activities. In this work, a separation strategy involving one-step macroporous resin adsorption chromatography combined with crystallization was established for BFA purification from Eupenicillium brefeldianum CCTCC M 208113 fermentation broth. Among six macroporous resin adsorbents tested, the non-polar resin HZ830 had the best adsorption and desorption performance. The static equilibrium adsorption data fitted well with the Freundlich equation, and the adsorption kinetic followed the pseudo-second order model. Through experimental optimization of column adsorption and desorption, BFA in purity of 90.4% (w/w), 92.1% (w/w) yield was obtained by a one-step macroporous resin adsorption chromatography, using a stepwise elution protocol. Furthermore, high purity (>99%, w/w) of BFA crystals were prepared from E. brefeldianum CCTCC M 208113 fermentation broth in an overall recovery of 67.0% (w/w), using a combination of adsorption chromatography packed with non-polar macroporous adsorbent HZ830 and crystallization in acetone.