A new family of sesterterpenoids isolated around the Pacific Rim

Shirley, Harry J.; Jamieson, Megan L.; Brimble, Margaret A.; Bray, Christopher D.

doi:10.1039/c7np00049a

Cited by 26 publications

(17 citation statements)

References 44 publications

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“…Marine organisms are the cradle of birth for many excellent pharmaceutical products (Blunt et al, 2017 ; Shirley et al, 2018 ). Endophytes dwelling inside the marine seaweeds is the treasure house of many medicinally important secondary metabolites.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative and Antioxidative Bioactive Compounds in Extracts of Marine-Derived Endophytic Fungus Talaromyces purpureogenus

et al. 2018

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Endophytic fungi are now recognized as sources of pharmacologically beneficial, novel bioactive compounds. This study was carried out to evaluate antiproliferative and antioxidative potential of a seaweed endophytic fungus Talaromyces purpureogenus. Extracts with different solvents of the fungus grown on different liquid media were assayed for the antiproliferative and antioxidative activities. Tested 6 cancer cell lines, the highest antiproliferative activity was observed in ethyl acetate extract of total culture grown in Potato Dextrose Broth for 28 days in a dose-dependent manner. The highest antioxidative activity was observed in hexane extract of fungal culture grown in Malt Extract Broth for 21 days. Analyzed for secondary metabolites, the extract revealed the presence of phenolics, alkaloids, flavonoids, steroids and terpenoids. Further, Gas Chromatography Mass Spectroscopy (GCMS) analysis of the extract revealed the presence of several compounds including 3-nitropropanoic acid, 4H-pyran-4-one 5-hydroxy-2-(hydroxymethyl), hexadecanoic acid, and octadecanoic acid, known to be cytotoxic or antioxidative. Among different cell lines tested, HeLa cells were the most vulnerable to the treatment of the fungal extract with an IC50 value of 101 ± 1 μg/mL. The extract showed no significant cytotoxicity to the normal human embryonic kidney cell line (HEK 293 T) in the MTT assay. The ethyl acetate extract induced membrane damage and mitochondrial depolarization and thereby apoptosis and cytotoxicity in HeLa cells. The study marks marine-derived endophytes as potential sources for discovery of novel drugs.

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Section: Discussionmentioning

confidence: 99%

Antiproliferative and Antioxidative Bioactive Compounds in Extracts of Marine-Derived Endophytic Fungus Talaromyces purpureogenus

et al. 2018

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“…Marine organisms are the cradle for many excellent pharmaceutical products, particularly soft corals [ 25 , 26 , 27 ]. Several types of cembranoid compounds with prominent biological activities have been isolated from Sinularia flexibilis [ 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Sandensolide Induces Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells and in Zebrafish Xenograft Model

Chen

Liu

et al. 2018

Marine Drugs

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Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates the effect of sandensolide, a cembrane isolated from Sinularia flexibilis, to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting. Both the in vitro bioassay and the zebrafish xenograft model demonstrated the anti-oral cancer effect of sandensolide. Moreover, sandensolide was able to significantly suppress colony formation and induce apoptosis, as well as cell cycle arrest, in OSCC by regulating multiple key proteins. Induction of reactive oxygen species (ROS) was observed in sandensolide-treated oral cancer cells. However, these apoptotic changes were rescued by NAC pretreatment. These findings contribute to the knowledge of the model of action of sandensolide, which may induce oxidative stress-mediated cell death pathways as a potential agent in oral cancer therapeutics.

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“…About 500 µL blood samples were collected at 0. 5,1,2,3,4,5,6,8,10,12,16,20,24,30 and 36 h into heparinized tubes after the intragastric administration of MHO7. All blood samples were immediately centrifuged at 8000 g for 5 min and the resulting plasma was transferred and then processed as described in sample preparation for the analysis by LC-MS/MS.…”

Section: Pharmacokinetic Studies Assaymentioning

confidence: 99%

“…Of the more than 80,000 identified terpenoids [1], sesterterpenoids are amongst the rarest and are an attractive source of leading compounds with little more than 1000 compounds known [2]. In recent years, amounts of biological sesterterpenoids were isolated from the metabolites of marine microorganism [3], such as neomangicols and mangicols from marine-derived fungus Fusarium sp.…”

Section: Introductionmentioning

confidence: 99%

Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus

Tian

Deng

et al. 2019

Marine Drugs

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Sesterterpene MHO7 derived from mangrove fungus is a novel estrogen receptor degrader for the treatment of breast cancer. To explore its safety and pharmacokinetics in vivo, Log P/D values, stability in simulated gastric/intestinal (SGF/SIF), toxicity, and pharmacokinetics studies were carried mainly by liquid chromatography technique coupled with tandem mass spectrometry (LC–MS/MS) method in mice, and the effect of MHO7 on mice gut microbiota at different time points was revealed by 16S rRNA sequencing. Log P/D values ranged 0.93–2.48, and the compound in SGF and SIF is stable under the concentration of 5 mM·L−1. The maximum tolerance dose (MTD) of oral administration in mice was 2400 mg·kg−1. The main pharmacokinetics parameters were as following: Cmax of 1.38 μg·mL−1, Tmax of 8 h, a half-life (t1/2) of 6.97 h, an apparent volume of mean residual time (MRT) of 8.76 h, and an area under the curve (AUC) of 10.50 h·μg·mL−1. MHO7 displayed a wide tissue distribution in mice, with most of the compound in liver (3.01 ± 1.53 μg·g−1) at 1 h, then in fat (5.20 ± 3.47 μg·g−1) at 4 h, and followed by reproductive organs with the concentrations of 23.90 ± 11.33 μg·g−1,13.69 ± 10.29 μg·g−1, 1.46 ± 1.23 μg·g−1, and 0.36 ± 0.46 μg·g−1 at 8, 12, 20 and 30 h, respectively. The most influenced genera of gut microbiome belonged to phylum Firmicutes (21 of 28), among which 18 genera originated from the order Clostridiales, class Clostridia, and families of Ruminococcaceae (11 of 18) and Lachnospiraceae (4 of 18). These results provide that MHO7 is suitable for oral administration in the treatment of breast cancer with the target organs of reproductive organs and regulation on Ruminococcaceae and Lachnospiraceae.

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A new family of sesterterpenoids isolated around the Pacific Rim

Cited by 26 publications

References 44 publications

Antiproliferative and Antioxidative Bioactive Compounds in Extracts of Marine-Derived Endophytic Fungus Talaromyces purpureogenus

Antiproliferative and Antioxidative Bioactive Compounds in Extracts of Marine-Derived Endophytic Fungus Talaromyces purpureogenus

Sandensolide Induces Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells and in Zebrafish Xenograft Model

Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus

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