Beshanzoides A–D, unprecedented cycloheptanone-containing polyketides from <i>Penicillium commune</i> P-4-1, an endophytic fungus of the endangered conifer <i>Abies beshanzuensis</i>

Chen, Haowei; Jiang, Chunxiao; Li, Jiyang; Li, Na; Zang, Yi; Wu, Xiying; Chen, Wenxue; Xiong, Juan; Li, Jia; Hu, Jin‐Feng

doi:10.1039/d1ra08377e

Cited by 13 publications

(6 citation statements)

References 42 publications

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“…Compounds 1 – 3 showed no optical activity in polarimeter and ECD analysis, which indicated that all the isolates are racemic mixtures. Compound 1 was previously reported to show spontaneous racemization of the phthalide scaffold, and similar phenomena were reported on other phthalides. − Our attempt on the chiral separation of compound 3 confirmed the equal amounts of enantiomers (Figure d); however, they could not be kept in enantiomerically pure form due to the fast rate of racemization. Thus, all the isolates were subjected to bioassays as racemic mixtures.…”

Section: Resultssupporting

confidence: 85%

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Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity

et al. 2023

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Endolichenic fungi (ELF) produce specialized metabolites that have various medicinal properties. Inhibition of tumor angiogenesis efficaciously suppresses many types of cancer. This study aimed to discover novel antiangiogenic agents from specialized metabolite extracts of ELF strains isolated from Korean lichens. The EtOAc extracts of 51 ELF strains were subjected to a screening pipeline consisting of cell viability, scratch wound healing, and Transwell migration assays. The EtOAc extract of Arthrinium sp. EL000127 showed the most potent inhibitory activity against the chemotactic migration of human umbilical vein endothelial cells (HUVEC). Targeted isolation on the major LC-MS peaks exhibited a previously known phthalide, 3-Omethylcyclopolic acid (1), and two unknown analogues of 1, 3-O-phenylethylcyclopolic acid (2) and 3-O-p-hydroxyphenylethylcyclopolic acid (3). The structures were characterized by MS and NMR analyses. All the isolates were acquired and applied to bioassays as racemates due to spontaneous racemization. Among the isolates, compound 3 effectively inhibits HUVEC motility by suppressing mRNA expressions of genes regulating epithelial cell survival and motility, which suggested that compound 3 is a potent antiangiogenic agent suitable for further exploration as a potential novel therapeutic against cancers.

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Section: Resultssupporting

confidence: 85%

“…Thus, all the isolates were subjected to bioassays as racemic mixtures. Based on the previously suggested mechanisms of phthalide racemization via aldehyde–carboxylic acid tautomers, , compounds 1 – 3 were proposed to racemize via their enol ether tautomers (Figure e).…”

Section: Resultsmentioning

confidence: 99%

Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity

et al. 2023

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“…Each species of Seiridium proved to produce at least one major toxin as well as several minor phytotoxic metabolites in vitro. In particular, S. cupressi proved to produce two major toxins, i.e., seiricuprolide (SCU), a 14-macrolide and cyclopaldic acid (CA) ( Figure 1 ), a pentasubstituted isobenzofuranone which was already known as an antifungal metabolite produced by some species of Aspergillus [ 2 , 3 ], Penicillium [ 4 , 5 ] and Pestalotiopsis sp. [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclopaldic Acid, the Main Phytotoxic Metabolite of Diplodia cupressi, Induces Programmed Cell Death and Autophagy in Arabidopsis thaliana

Samperna

Masi

Vurro

et al. 2022

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Cyclopaldic acid is one of the main phytotoxic metabolites produced by fungal pathogens of the genus Seiridium, causal agents, among others, of the canker disease of plants of the Cupressaceae family. Previous studies showed that the metabolite can partially reproduce the symptoms of the infection and that it is toxic to different plant species, thereby proving to be a non-specific phytotoxin. Despite the remarkable biological effects of the compound, which revealed also insecticidal, fungicidal and herbicidal properties, information about its mode of action is still lacking. In this study, we investigated the effects of cyclopaldic acid in Arabidopsis thaliana plants and protoplasts, in order to get information about subcellular targets and mechanism of action. Results of biochemical assays showed that cyclopaldic acid induced leaf chlorosis, ion leakage, membrane-lipid peroxidation, hydrogen peroxide production, inhibited root proton extrusion in vivo and plasma membrane H+-ATPase activity in vitro. qRT-PCR experiments demonstrated that the toxin elicited the transcription of key regulators of the immune response to necrotrophic fungi, of hormone biosynthesis, as well as of genes involved in senescence and programmed cell death. Confocal microscopy analysis of protoplasts allowed to address the question of subcellular targets of the toxin. Cyclopaldic acid targeted the plasma membrane H+-ATPase, inducing depolarization of the transmembrane potential, mitochondria, disrupting the mitochondrial network and eliciting overproduction of reactive oxygen species, and vacuole, determining tonoplast disgregation and induction of vacuole-mediated programmed cell death and autophagy.

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“…Recently, an ACL inhibitor, bempedoic acid, was approved for the treatment of hypercholesterolemic patients as monotherapy or in combination with ezetimibe (Delevry and Gupta, 2021;Sansenya and Payaka, 2022). Additionally, it was reported that polyketides have exhibited potential α-glucosidase and ACL inhibitory activities (Chen et al, 2021;Paulose and Chakraborty, 2022;Zhong et al, 2022). Thus, discovery of new polyketides with potential α-glucosidase and ACL inhibitory activities shows great promise for the development of new agents for the treatment of metabolic diseases.…”

Section: Introductionmentioning

confidence: 99%

Citrinin Derivatives From Penicillium Citrinum Y34 That Inhibit α-Glucosidase and ATP-Citrate Lyase

et al. 2022

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Two new citrinin dimers bearing a 6,6-spiroketal moiety (1 and 2) and four known analogues (3–6), together with 18 known citrinin monomers (7–24), were isolated from the culture of hydrothermal vent-associated fungus Penicillium citrinum Y34. Their structures were identified by extensive spectroscopic analyses, 13C NMR calculation in combination with DP4+, linear correlation coefficient (R2), and mean absolute error (MAE) values analyses, and electronic circular dichroism (ECD) calculation. The α-glucosidase and ATP-citrate lyase (ACL) inhibitory activities of isolated compounds were evaluated. Compounds 1, 3, and 12 displayed moderate α-glucosidase inhibitory activities with IC50 values of 239.8, 176.2, and 424.4 μM, respectively. Enzyme kinetics investigations of 1 and 3 suggested their non-competitive inhibition of α-glucosidase with Ki values of 204.3 and 212.7 μM, respectively. Meanwhile, compound 4 showed significant ACL inhibitory potential with an IC50 value of 17.4 μM. Furthermore, the interactions of 1, 3, and 12 with α-glucosidase and 4 with ACL were investigated by molecular docking assay. This study demonstrates that citrinins, especially for their dimers, could be potential lead compounds for the development of new agents for the treatment of metabolic diseases.

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Beshanzoides A–D, unprecedented cycloheptanone-containing polyketides from Penicillium commune P-4-1, an endophytic fungus of the endangered conifer Abies beshanzuensis

Abstract: Four unprecedented cycloheptanone-containing and some related known bioactive polyketides were isolated from an endophytic fungus associated with the critically endangered conifer Abies beshanzuensis.

Cited by 13 publications

References 42 publications

Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity

Phthalides Isolated from the Endolichenic Arthrinium sp. EL000127 Exhibits Antiangiogenic Activity

Cyclopaldic Acid, the Main Phytotoxic Metabolite of Diplodia cupressi, Induces Programmed Cell Death and Autophagy in Arabidopsis thaliana

Citrinin Derivatives From Penicillium Citrinum Y34 That Inhibit α-Glucosidase and ATP-Citrate Lyase

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