Fatima Nighat, Sripisut Tawanun, Youn Ui J, Ahmed Safia, Ul-Haq Ihsan, Munoz-Acuna Ulyana, Simmons Charles J, Qazi Muneer A, Jadoon Muniba, Tan Ghee T, de Blanco Esperanza J C, Chang Leng C
Department of Pharmacy, COMSATS Institute of Information Technology (CIIT), Abbottabad. Pakistan.
School of Cosmetic Science, Mae Fah Luang University, Tasud, Muang, Chiang Rai 57100. Thailand.
Med Chem. 2017;13(7):689-697. doi: 10.2174/1573406413666170216145121.
Endophytic fungi are being recognized as vital and untapped sources of a variety of structurally novel and unique bioactive secondary metabolites in the field of natural products drug discovery. Herein, this study reports the isolation and characterization of secondary metabolites from an endophytic fungus Penicillium polonicum (NFW9) associated with Taxus fuana.
The extracts of the endophytic fungus cultured on potato dextrose agar were purified using several chromatographic techniques. Biological evaluation was performed based on their abilities to inhibit tumor necrosis factor-alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) and cytotoxicity assays.
Bioactivity-directed fractionation of the ethyl acetate extract of a fermentation culture of an endophytic fungus, Penicillium polonicum led to the isolation of a dimeric anthraquinone, (R)- 1,1',3,3',5,5'-hexahydroxy-7,7'-dimethyl[2,2'-bianthracene]-9,9',10,10'-tetraone (1), a steroidal furanoid (-)-wortmannolone (2), along with three other compounds (3-4). Moreover, this is the first report on the isolation of compound 1 from an endophytic fungus. All purified metabolites were characterized by NMR and MS data analyses. The stereo structure of compound 1 was determined by the measurement of specific optical rotation and CD spectrum. The relative stereochemistry of 2 was confirmed by single-crystal X-ray diffraction. Compounds 2-3 showed inhibitory activities in the TNF-α-induced NF-κB assay with IC50 values in the range of 0.47-2.11 µM. Compounds 1, 4 and 5 showed moderate inhibition against NF-κB and cancer cell lines.
The endophytic fungus Penicillium polonicum of Taxus fuana is capable of producing biologically active natural compounds. Our results provide a scientific rationale for further chemical investigations into endophyte-producing natural products, drug discovery and development.
在天然产物药物发现领域，内生真菌正被视为各种结构新颖独特的生物活性次生代谢产物的重要且未被开发的来源。在此，本研究报道了从与南方红豆杉相关的内生真菌波兰青霉（NFW9）中分离和鉴定次生代谢产物。
在马铃薯葡萄糖琼脂上培养的内生真菌提取物通过多种色谱技术进行纯化。基于其抑制肿瘤坏死因子-α（TNF-α）诱导的核因子-κB（NF-κB）的能力和细胞毒性测定进行生物学评价。
对内生真菌波兰青霉发酵培养物的乙酸乙酯提取物进行生物活性导向分级分离，得到一种二聚蒽醌，（R）-1,1',3,3',5,5'-六羟基-7,7'-二甲基[2,2'-联蒽]-9,9',10,10'-四酮（1），一种甾体呋喃类（-）-渥曼青霉素（2），以及其他三种化合物（3 - 4）。此外，这是首次从内生真菌中分离出化合物1。所有纯化的代谢产物通过核磁共振（NMR）和质谱（MS）数据分析进行表征。化合物1的立体结构通过比旋光度测量和圆二色光谱（CD）确定。化合物2的相对立体化学通过单晶X射线衍射得到证实。化合物2 - 3在TNF-α诱导的NF-κB测定中表现出抑制活性，IC50值在0.47 - 2.11 μM范围内。化合物1、4和5对NF-κB和癌细胞系表现出中等抑制作用。
南方红豆杉的内生真菌波兰青霉能够产生具有生物活性的天然化合物。我们的结果为进一步对内生菌产生的天然产物进行化学研究、药物发现和开发提供了科学依据。
