Abstract:
Endophytic fungi are important sources of anticancer compounds. An endophytic fungus was isolated from the medicinal plant Achyrocline satureioides, and molecularly identified as Biscogniauxia sp. (family Xylariaceae) based on partial nucleotide sequences of the internal transcribed spacer genomic region (GenBank Accession No. ON257911). The chemical characterization and cytotoxic properties of secondary metabolites produced by Biscogniauxia sp. were evaluated in a human melanoma cell line (A375). The fungus was grown in potato-dextrose liquid medium for 25 days, and the extracted compounds were subjected to solid-phase fractionation to obtain the purified FDCM fraction, for which the metabolites were elucidated via ultra-performance chromatography coupled to a mass spectrometer. In the present study, 17 secondary metabolites of Biscogniauxia sp., including nine polyketide derivatives, five terpenoids, and three isocoumarins, were putatively identified. This is the first study to report of the ability of Biscogniauxia sp. in the production of isocoumarin orthosporin; the terpenoids nigriterpene A and 10-xylariterpenoid; the polyketide derivatives daldinin C, 7\'dechloro-5\'-hydroxygriseofulvin, daldinone D, Sch-642305, curtachalasin A, cytochalasin E, epoxycytochalasins Z8, Z8 isomer, and Z17. Furthermore, this study has reported the biosynthesis of Sch-642305 by a Xylariaceae fungus for the first time. FDCM significantly reduced the viability and proliferation of human melanoma cells at half-maximal inhibitory concentrations of 10.34 and 6.89 µg/mL, respectively, and induced late apoptosis/necrosis and cell cycle arrest in G2/M phase after 72 h of treatment. Given its ability to produce unique metabolites with promising cytotoxic effects, Biscogniauxia sp. of A. satureioides may be a reservoir of compounds with important therapeutic applications.
摘要:
内生真菌是抗癌化合物的重要来源。从药用植物Achyroclinesatureioides中分离出内生真菌,并在分子上鉴定为Biscogniauxiasp。(木脂科)基于内部转录间隔区基因组区域的部分核苷酸序列(GenBank登录号ON257911)。Bisconiauxiasp。产生的次级代谢产物的化学性质和细胞毒性。在人黑素瘤细胞系(A375)中进行评估。真菌在马铃薯-葡萄糖液体培养基中生长25天,并将提取的化合物进行固相分馏以获得纯化的FDCM馏分,通过与质谱仪耦合的超高效色谱法阐明了代谢物。在本研究中,Biscogniauxiasp的17次生代谢产物。,包括九种聚酮衍生物,五种萜类化合物,和三种异香豆素,被推定确定。这是第一个报告双冠花能力的研究。在异香豆素原孢子素的生产中;萜类化合物黑萜A和10-木二萜;聚酮化合物衍生物daldininC,7\'dechloro-5\'-羟基灰黄霉素,daldinoneD,Sch-642305,尚切拉辛A,细胞松弛素E,环氧细胞松弛素Z8,Z8异构体,Z17此外,这项研究首次报道了木参科真菌对Sch-642305的生物合成。FDCM在10.34和6.89µg/mL的半最大抑制浓度下显着降低了人类黑色素瘤细胞的活力和增殖。分别,治疗72h后,在G2/M期诱导晚期凋亡/坏死和细胞周期停滞。鉴于其能够产生具有有希望的细胞毒性作用的独特代谢物,双眼花。satureioides的可能是具有重要治疗应用的化合物的储库。