Meroterpenoids from Neosetophoma sp.: A Dioxa\[4.3.3\]propellane Ring System, Potent Cytotoxicity, and Prolific Expression

Our plain-English summary of Meroterpenoids from Neosetophoma sp.: A Dioxa[4.3.3]propellane Ring System, Potent Cytotoxicity, and Prolific Expression, by T. El-Elimat, H.A. Raja, S. Ayers, et al (Organic Letters, 2019).

The study

• Authors: T. El-Elimat, H.A. Raja, S. Ayers, S.J. Kurina, J.E. Burdette, Z. Mattes, R. Sabatelle, J.W. Bacon, A.H. Colby, M.W. Grinstaff, C.J. Pearce, N.H. Oberlies
• Journal: Organic Letters
• Published: 2019;21(2):529-534
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Six fungal metabolites, of which five were new, including one (1) with a dioxa[4.3.3]propellane ring system, were discovered, identified, and structurally elucidated from Neosetophoma sp. (strain MSX50044); these compounds are similar to the bis-tropolone, eupenifeldin. Three of the meroterpenoids are potent cytotoxic agents against breast, ovarian, mesothelioma, and lung cancer cells with nanomolar IC50 values while not inducing mitochondrial toxicity at 12.5 μM.

In plain English

This laboratory chemistry study did not examine asbestos or exposed people. The authors grew a fungus, Neosetophoma sp. (strain MSX50044), on rice and isolated six related natural compounds called meroterpenoids, five of them new. One of them, named neosetophomone A, had a ring structure (a dioxa[4.3.3]propellane) that the authors described as the first report of its kind. They tested the compounds on laboratory-grown cancer cells, including a human mesothelioma cell line (MSTO-211H) and breast, ovarian and lung cancer cell lines. Compound 3, the known compound eupenifeldin, was the most potent. The concentration needed to cut cell growth to half of untreated cells over 72 hours was 80 nM for the mesothelioma cells. Across the six cell lines it ranged from 10 nM (mouse lung cancer cells) to 2830 nM (human breast cancer cells). In a laboratory test, compounds 1 to 3 showed no toxicity to mitochondria up to 12.5 μM, the highest concentration tested. Eupenifeldin made up more than 28% of the dried organic extract. The authors concluded that this ample supply opens the door to further studies to enhance activity and optimize delivery.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory chemistry study: isolation and structure determination of fungal compounds, followed by tests on cancer cell lines and a mitochondrial toxicity test (in vitro)
• Who was studied: No people were studied. The fungus Neosetophoma sp. (strain MSX50044) was grown on rice. The compounds were tested on six cancer cell lines: MDA-MB-231 (human breast), OVCAR-3 and OVCAR-8 (human ovarian), MSTO-211H (human mesothelioma), LLC (murine lung) and A549 (human lung).
• Exposure: No asbestos exposure was studied. Cancer cells were treated with six compounds isolated from the fungus (compounds 1 to 6), with Taxol listed for comparison. Growth inhibition was measured after a 72-hour incubation.
• Main results:
  • Six meroterpenoids were isolated from the fungus. Five were new, and one (compound 1, neosetophomone A) had a dioxa[4.3.3]propellane ring system.
  • Compound 3 (eupenifeldin) was the most potent. Its IC50 values were 2830 nM (MDA-MB-231 breast), 330 nM (OVCAR-3 ovarian), 20 nM (OVCAR-8 ovarian), 80 nM (MSTO-211H mesothelioma), 10 nM (LLC mouse lung) and 1330 nM (A549 lung). Compound 4 was next most potent.
  • Compounds 1 to 3 were tested for mitochondrial toxicity in vitro. No toxicity was seen up to the highest concentration tested, 12.5 μM.
  • The fungus produced compound 3 at a yield exceeding 28% of the dried organic extract.
• The authors' conclusion: The authors concluded that compound 3 was the most potent against the panel of cell lines and did not show toxicity to mitochondria. They stated that the ample supply of this compound opens the door for further studies to enhance its activity and optimize delivery.
• Limitations the authors state:
  • The authors were unable to assign the absolute configuration (3-D arrangement) of compounds 5 and 6 using Mosher's ester method.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Lung Cancer.

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