New Ophiobolin Derivatives from the Marine Fungus Aspergillus flocculosus and Their Cytotoxicities against Cancer Cells

Choi, Byeoung Kyu; Trinh, Phan Thi Hoai; Lee, Hwa Sun; Kang, Jong Soon; Ngoc, Ngo Thi Duy; Vân, Trần Thị Thanh; Shin, Hee Jae

doi:10.3390/md17060346

Cited by 38 publications

(31 citation statements)

References 23 publications

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“…The fungus Aspergillus flocculosus 168ST-16.1 was isolated from the algae Padina sp., collected using SCUBA at a depth of 10 m in Son Tra peninsular, Da Nang, Vietnam and cultured on rice media at 28 °C for three weeks in Erlenmeyer flasks, each containing rice, yeast extract, KH 2 PO 4 , and natural sea water as previously described [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Two New Phomaligols from the Marine-Derived Fungus Aspergillus flocculosus and Their Anti-Neuroinflammatory Activity in BV-2 Microglial Cells

et al. 2021

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Two new phomaligols, deketo-phomaligol A (1) and phomaligol E (2), together with six known compounds (3–8) were isolated from the culture broth of the marine-derived fungus Aspergillus flocculosus. Compound 1 was first isolated as a phomaligol derivative possessing a five-membered ring. The structures and absolute configurations of the new phomaligols were determined by detailed analyses of mass spectrometry (MS), nuclear magnetic resonance (NMR) data, optical rotation values and electronic circular dichroism (ECD). In addition, the absolute configurations of the known compounds 3 and 4 were confirmed by chemical oxidation and comparison of optical rotation values. Isolated compounds at a concentration of 100 μM were screened for inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among the compounds, 4 showed moderate anti-neuroinflammatory effects with an IC50 value of 56.6 μM by suppressing the production of pro-inflammatory mediators in activated microglial cells without cytotoxicity.

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Section: Methodsmentioning

confidence: 99%

Two New Phomaligols from the Marine-Derived Fungus Aspergillus flocculosus and Their Anti-Neuroinflammatory Activity in BV-2 Microglial Cells

et al. 2021

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“…Many isolated metabolites were aromatic compounds, i.e., phenalenones (190)(191)(192)(193)(194)(195)(196)(197)(198), grisane metabolites (199)(200)(201), and azaphilones . Linear polyketides with various side chains and other polyketides (246)(247)(248)(249)(250)(251)(252)(253)(254)(255)(256)(257) were also obtained.…”

Section: Other Polyketidesmentioning

confidence: 99%

“…Six new sesquiterpenes ( 338 – 342 ) and four known sesquiterpenes ( 343 – 346 ) [ 256 ], which belonged to the ophioboline family, were isolated from marine endophyte Aspergillus flocculosus [ 255 ]. All the isolated compounds showed strong cytotoxic activity.…”

Section: Terpenoids Steroids and Related Compoundsmentioning

confidence: 99%

Antibiotics from Extremophilic Micromycetes

et al. 2020

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Extremophilic microorganisms, which are capable of functioning normally at extremely high or low temperatures, pressure, and in other environmental conditions, have been in the focus of microbiologists’ attention for several decades due to the biotechnological potential of enzymes inherent in extremophiles. These enzymes (also called extremozymes) are used in the production of food and detergents and other industries. At the same time, the inhabitants of extreme econiches remained almost unexplored for a long time in terms of the chemistry of natural compounds. In recent years, the emergence of new antibiotic-resistant strains of pathogens, which affect humans and animals has become a global problem. The problem is compounded by a strong slowdown in the development of new antibiotics. In search of new active substances and scaffolds for medical chemistry, researchers turn to unexplored natural sources. In recent years, there has been a sharp increase in the number of studies on secondary metabolites produced by extremophiles. From the discovery of penicillin to the present day, micromycetes, along with actinobacteria, are one of the most productive sources of antibiotic compounds for medicine and agriculture. Many authors consider extremophilic micromycetes as a promising source of small molecules with an unusual mechanism of action or significant structural novelty. This review summarizes the latest (for 2018–2019) experimental data on antibiotic compounds, which are produced by extremophilic micromycetes with various types of adaptation. Active metabolites are classified by the type of structure and biosynthetic origin. The data on the biological activity of the isolated metabolites are summarized.

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“…Ophiobolins (Ophs) are a very rare group of sesterterpenoids that bear a unique 5-8-5 tricarbocyclic in structure [5]. At present, 72 Ophs have been reported including 35 Ophs which were produced by marine-derived fungus [5,[7][8][9]. The family shows significant inhibitory effects on the growth of a variety of cancer cells, drug-resistant cells, and cancer stem cells [5].…”

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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New Ophiobolin Derivatives from the Marine Fungus Aspergillus flocculosus and Their Cytotoxicities against Cancer Cells

Cited by 38 publications

References 23 publications

Two New Phomaligols from the Marine-Derived Fungus Aspergillus flocculosus and Their Anti-Neuroinflammatory Activity in BV-2 Microglial Cells

Two New Phomaligols from the Marine-Derived Fungus Aspergillus flocculosus and Their Anti-Neuroinflammatory Activity in BV-2 Microglial Cells

Antibiotics from Extremophilic Micromycetes

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

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