Mycoepoxydiene represents a novel class of fungal metabolites

doi:10.1016/S0040-4039(98)02700-2

Tetrahedron Letters

Volume 40, Issue 8, 19 February 1999, Pages 1479-1482

https://doi.org/10.1016/S0040-4039(98)02700-2 Get rights and content

Abstract

A novel epoxycyclooctadiene-δ-lactone, mycoepoxydiene, was isolated from a fungal culture (OS-F66617). Its structure and relative stererochemistry were established using spectroscopic studies, including single-crystal X-ray diffraction analysis.

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Oxygen-bridged cyclooctadienes and other polyketides from the mangrove endophytic fungus Diaporthe sp. ZJHJYZ-1
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Nine oxygen-bridged cyclooctadienes (1 – 9), including four undescribed previously (1, 2, 5, and 6), together with a new cyclohexanone derivative (10) and a new oxaspiroundecanone derivative (11), were isolated from the mangrove endophytic fungus Diaporthe sp. ZJHJYZ-1. The structures of compounds were elucidated via detailed NMR, HR-ESI-MS analyses, ECD spectra calculation, ¹H - ¹H coupling constants comparison and X-ray single-crystal diffraction analysis. In bioassays, compound 8 significantly suppressed six human cancer cell lines, MDA-MB-231, MDA-MB-435, HCT116, A549, SNB19, and PC3, with IC₅₀ values in the range of 1.97 ± 0.01 – 19.17 ± 1.02 μM. And compound 10 promisingly inhibited MDA-MB-231 and PC3 with IC₅₀ values of 2.54 ± 1.23 and 22.07 ± 0.64 μM, respectively.
Antitumor and immunomodulatory compounds from fungi
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With its pervasive presence in every environment on earth, the kingdom of fungi represents one of the most prolific natural sources of bioactive products to be considered for pharmaceutical exploitation. Particularly, many “small” secondary metabolites of these microorganisms, basically serving as chemical messengers in the regulation of relationships with their biocenotic associates, result to possess a bioactivity profile which may qualify them as prospect antitumor and/or immunomodulatory drugs. Occurrence, structural diversity and mechanisms of action of these compounds are reviewed in this article in view of possible applications in human medicine.
Bioactive oxygen-bridged cyclooctadienes from endophytic fungus Phomopsis sp. BCC 45011
2015, Tetrahedron
Citation Excerpt :
Mycoepoxydiene (1) was the first compound in this class reported so far. It was first isolated from a fungus OS-F66617 in 19991 and has been reported to have antimicrobial and anticancer activities.2–4 Other compounds in this family include deacetylmycoepoxydiene (2) and 2,3-dihydro mycoepoxydiene from the endophytic fungus Phomopsis sp.
Three new oxygen-bridged cyclooctadiene containing compounds, 5–7, phomoxydienes A–C, and two new dothiorelones I (8) and J (9), together with 10 known compounds were isolated from endophytic fungus, Phomopsis sp. BCC 45011. Structures were determined by NMR spectroscopic and MS spectrometric analyses. Mycoepoxydiene (1), deacetylmycoepoxydiene (2), phomoxydienes A (5) and C (7), and cytosporone E (12) displayed antimalarial and cytotoxic activities while 1893 A (3) and cytosporone P (13) showed only cytotoxic and antimalarial activity, respectively.
Deacetyl-mycoepoxydiene, isolated from plant endophytic fungi Phomosis sp. demonstrates anti-microtubule activity in MCF-7 cells
2015, Biomedicine and Pharmacotherapy
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HLY-1, which is found in submerged, rotting leaves of Kandelia candel in the mangrove forest in Fujian Province, China [18]. This compound shows similar cytotoxicity to human tumor cell lines with an IC50 ranging from 2.4 to 21.5 μM [8,19,20]. Treatment with mycoepoxydiene leads to a series of cellular events that includes cytoskeletal rearrangement and cell cycle arrest at the G2/M phase.
Deacetyl-mycoepoxydiene (DM), a novel secondary metabolite produced by the plant endophytic fungi Phomosis sp., induced the reorganization of cytoskeleton in actively growing MCF-7 cells by promoting polymerization of tubulin. DM could induce cell cycle arrest at G2/M in MCF-7 cells. Additionally, DM-induced apoptosis was characterized with up-regulating caspase-3, Bax, caspase-9, parp, and p21 while down-regulating Bcl-2 activation. DM conferred dose- and time-dependent inhibitory effects upon cell proliferation of MCF-7 cells both in cultured cells and nude mice with human breast carcinoma xenografts. The results obtained from these in vitro and in vivo models provide new data revealing the potential for DM as a novel microtubule inhibitor.
A rapid and sensitive LC-MS/MS assay for the quantitation of deacetyl mycoepoxydiene in rat plasma with application to preclinical pharmacokinetics studies
2012, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Citation Excerpt :
A123. It was first isolated in 2003 [1–5]. Appropriate analytical method is an urgent need to study its pharmacokinetics in vivo.
The purpose of this study was to develop and validate a high-performance liquid chromatographic–tandem mass spectrometric (LC–MS/MS) method for analysis of the deacetyl mycoepoxydiene in rat plasma. The analyte and internal standard (I.S.), benorilate, were extracted from rat plasma by precipitation protein and separated on a C₁₈ column using acetonitrile–0.5% formic acid as mobile phase. Detection was performed using a turbo-spray ionization source and mass spectrometric positive multi-reaction-monitoring-mode (+MRM) at an ion voltage of +4800 V. The assay was linear over the concentration range 5–5000 ng/mL with the lowest limit of quantification (LLOQ) of 5 ng/mL. The method also afforded satisfactory results in terms of the sensitivity, specificity, precision (intra- and inter-day, RSD < 5.8%), accuracy, recovery as well as the stability of the analyte under various conditions. The method was successfully applied to a preclinical pharmacokinetic study in rats after a single intravenous administration of deacetyl mycoepoxydiene 10 mg/kg.
Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the G2/M phase and apoptosis in HeLa cells
2010, Bioorganic and Medicinal Chemistry Letters
Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. It contains an oxygen-bridged cyclooctadiene core and an α,β-unsaturated δ-lactone moiety. MED induced the reorganization of cytoskeleton in actively growing HeLa cells by promoting formation of actin stress fiber and inhibiting polymerization of tubulin. MED could induce cell cycle arrest at G2/M in HeLa cells. MED-associated apoptosis was characterized by the formation of fragmented nuclei, PARP cleavage, cytochrome c release, activation of caspase-3, and an increased proportion of sub-G1 cells. Additionally, MED activated MAPK pathways. Interestingly, the time of JNK, p38, and Bcl-2 activation did not correlate with the release of cytochrome c. This study is the first report demonstrating the action mechanism of MED against tumor cell growth. These results provide the potential of MED as a novel low toxic antitumor agent.

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Mycoepoxydiene represents a novel class of fungal metabolites

Abstract

Phytochemistry

Phytochemistry

J. Nat. Prod.