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Cytotoxic metabolites from the endophytic fungus Chaetomium globosum 7951.

ABSTRACT: The following compounds were isolated from acetate extracts of Chaetomium globosum 7951 solid cultures: demethylchaetocochin C (1) and chaetoperazine A (3), two new epipolythiodioxopiperazine (ETP) alkaloids, a novel pyridine benzamide, 4-formyl-N-(3'-hydroxypyridin-2'-yl) benzamide (6), and three known ETP derivatives (2, 4, and 5). The structures of these compounds were determined using extensive spectroscopic data analysis. Compounds 1-3, and 6, inhibited the growth of MCF-7, MDA-MB-231, H460 and HCT-8 cells with an IC₅₀ of 4.5 to 65.0 μM.

SUBMITTER: Wang F

PROVIDER: S-EPMC9064350 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Cytotoxic metabolites from the endophytic fungus Chaetomium globosum 7951.

Wang Fang F Zhao Wuli W Zhang Conghui C Chang Shanshan S Shao Rongguang R Xing Jianguo J Chen Minghua M Zhang Yixuan Y Si Shuyi S

RSC advances 20190521 28

The following compounds were isolated from acetate extracts of Chaetomium globosum 7951 solid cultures: demethylchaetocochin C (1) and chaetoperazine A (3), two new epipolythiodioxopiperazine (ETP) alkaloids, a novel pyridine benzamide, 4-formyl-N-(3'-hydroxypyridin-2'-yl) benzamide (6), and three known ETP derivatives (2, 4, and 5). The structures of these compounds were determined using extensive spectroscopic data analysis. Compounds 1-3, and 6, inhibited the growth of MCF-7, MD ...[more]

PMID: 35521380

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Project description:The aim of the present study was to investigate the anti-rheumatoid activity of secondary metabolites produced by endophytic mycobiota in Egypt. A total of 27 endophytic fungi were isolated from 10 dominant medicinal plant host species in Wadi Tala, Saint Katherine Protectorate, arid Sinai, Egypt. Of those taxa, seven isolates of Chaetomium globosum (CG1-CG7), being the most frequent taxon, were recovered from seven different host plants and screened for production of active anti-inflammatory metabolites. Isolates were cultivated on half - strength potato dextrose broth for 21 days at 28°C on a rotatory shaker at 180 rpm, and extracted in ethyl acetate and methanol, respectively. The probable inhibitory effects of both extracts against an adjuvant induced arthritis (AIA) rat model were examined and compared with the effects of methotrexate (MTX) as a standard disease-modifying anti-rheumatoid drug. Disease activity and mobility scoring of AIA, histopathology and transmission electron microscopy (TEM) were used to evaluate probable inhibitory roles. A significant reduction (P < 0.05) in the severity of arthritis was observed in both the methanolic extract of CG6 (MCG6) and MTX treatment groups 6 days after treatment commenced. The average arthritis score of the MCG6 treatment group was (10.7 ± 0.82) compared to (13.8 ± 0.98) in the positive control group. The mobility score of the MCG6 treatment group (1.50 ± 0.55) was significantly lower than that of the positive control group (3.33 ± 0.82). In contrast, the ethyl acetate extract of CG6 (EACG6) treatment group showed no improvements in arthritis and mobility scores in AIA model rats. Histopathology and TEM findings confirmed the observation. Isolate CG6 was subjected to sequencing for confirmation of phenotypic identification. The internal transcribed spacer (ITS) 1-5.8 s - ITS2 rDNA sequences obtained were compared with those deposited in the GenBank Database and registered with accession number KC811080 in the NCBI Database. The present study revealed that the methanol extract of endophytic fungus C. globosum (KC811080) recovered from maidenhair fern has an inhibitory effect on inflammation, histopathology and morphological features of rheumatoid arthritis in an AIA rat model.

Project description:Endophytic fungi are effective in plant growth and development by secreting various kinds of plant hormones and nutrients. However, the cellular and molecular interactions between the endophytic fungi and plant growth-promoting have remained less explored. The present study was designed to explore the effects of the infection and colonization events of Chaetomium globosum strain ND35 on cucumber growth and the expression pattern of some metabolically important genes in development of the cucumber radicle. The results demonstrated that strain ND35 can infect and colonize the outer layers (cortical cells) of cucumber root and form a symbiotic structure with the host cell, similar to a periarbuscular membrane and establish chemical communication with the plant. Through transcriptome analysis, we found the differentially expressed genes (DEGs) caused by strain ND35 were mainly enriched in phenylpropanoid biosynthesis, plant hormone signal transduction, plant-pathogen interaction and photosynthesis. Correspondingly, the contents of reactive oxygen species (ROS), hydrogen peroxide (H2O2), indole-3-acetic acid (IAA), gibberellin (GA), zeatin (ZT), salicylic acid (SA), jasmonic acid (JA) and the activity of phenylalanine ammonia lyase (PAL), 4-coumarate-CoA ligase (4CL), cinnamyl alcohol dehydrogenase (CAD), and peroxidase (POD) in ND35-colonized seedlings were generally higher than those of non-inoculated seedlings. Overall, the infection and colonization events of C. globosum strain ND35 increased cucumber growth through complex regulation of plant hormones biosynthesis and metabolism. Furthermore, although the endophytic fungus strain ND35 produced IAA, GA, ZT, and ergosterol in the fermentation broth, and there are enabled to promote growth of cucumber, it is uncertain whether there are ND35-derived microbial hormones in plants. This study of the interaction between cucumber and strain ND35 contributes to a better understanding of the plant-endophytic fungi interactions, and may help to develop new strategies for crop production.

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Cytotoxic metabolites from the endophytic fungus Chaetomium globosum 7951.

Publications

Cytotoxic metabolites from the endophytic fungus <i>Chaetomium globosum</i> 7951.

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