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曼陀罗内生真菌粗提物对 A549 肺癌和 UMG87 神经胶质瘤细胞系的细胞毒性活性及基于 LC-QTOF-MS/MS 的代谢产物分析

Cytotoxic activity of crude extracts from Datura stramonium's fungal endophytes against A549 lung carcinoma and UMG87 glioblastoma cell lines and LC-QTOF-MS/MS based metabolite profiling.

机构信息

Department of Biotechnology and Food Technology, Faculty of Science, University of Johannesburg, Box 17011, Doornfontein, Johannesburg, PO, 2028, South Africa.

South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.

出版信息

BMC Complement Altern Med. 2019 Nov 21;19(1):330. doi: 10.1186/s12906-019-2752-9.

Abstract

BACKGROUND

Endophytic fungi are a proven source of bioactive secondary metabolites that may provide lead compounds for novel drug discovery. In this study, crude extracts from fungal endophytes isolated from Datura stramonium were evaluated for cytotoxic activity on two human cancer cell lines.

METHODS

Fungal endophytes were isolated from surface sterilized aerial parts of D. stramonium and identified using molecular, morphological and phylogenetic methods. Ethyl acetate crude extracts from these isolates were evaluated for cytotoxic activity on A549 lung carcinoma and UMG87 glioblastoma cell lines. Metabolite profiling was then performed by liquid chromatography coupled to quadrupole time-of-flight with tandem mass spectrometry (LC-QTOF-MS/MS) for the cytotoxic crude extract.

RESULTS

Eleven fungal endophytes were identified from D. stramonium. Significant cytotoxicity was only observed from the crude extract of Alternaria sp. KTDL7 on UMG87 glioblastoma cells (IC = 21.49 μg/ml). Metabolite profiling of this crude extract tentatively revealed the presence of the following secondary metabolites: 1,8-dihydroxynaphthalene (1), anserinone B (2), phelligridin B (3), metacytofilin (4), phomopsidin (5) and vermixocin A (6). Compounds 2 and 3 have been shown to be cytotoxic in literature.

CONCLUSION

The findings in this study suggest that the crude extract of Alternaria sp. KTDL7 possesses compound(s) cytotoxic to glioblastoma multiforme cells. Future studies to isolate and characterize the cytotoxic compound(s) from this fungus could result in lead development of a fungal-based drug for glioblastoma multiforme treatment.

摘要

背景

内共生真菌是生物活性次生代谢产物的可靠来源,可为新型药物发现提供先导化合物。在这项研究中,评估了从曼陀罗中分离的真菌内共生菌的粗提物对两种人类癌细胞系的细胞毒性活性。

方法

从曼陀罗表面消毒的地上部分分离真菌内共生体,并使用分子、形态和系统发育方法进行鉴定。评估这些分离物的乙酸乙酯粗提物对 A549 肺癌和 UMG87 神经胶质瘤细胞系的细胞毒性活性。然后通过液相色谱-四极杆飞行时间串联质谱(LC-QTOF-MS/MS)对细胞毒性粗提取物进行代谢物分析。

结果

从曼陀罗中鉴定出 11 种真菌内共生体。只有Alternaria sp. KTDL7 的粗提取物对 UMG87 神经胶质瘤细胞表现出显著的细胞毒性(IC = 21.49 μg/ml)。该粗提取物的代谢物分析初步表明存在以下次生代谢物:1,8-二羟基萘(1)、anserinone B(2)、phelligridin B(3)、metacytofilin(4)、phomopsidin(5)和vermixocin A(6)。文献表明化合物 2 和 3 具有细胞毒性。

结论

本研究结果表明,Alternaria sp. KTDL7 的粗提取物具有对多形性胶质母细胞瘤细胞的细胞毒性化合物。未来从该真菌中分离和鉴定细胞毒性化合物的研究可能会导致基于真菌的胶质母细胞瘤多形性药物的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87ec/6873518/2fdfe4926bc8/12906_2019_2752_Fig1_HTML.jpg

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