Structures of Nahuoic Acids B-E Produced in Culture by a Streptomyces sp. Isolated from a Marine Sediment and Evidence for the Inhibition of the Histone Methyl Transferase SETD8 in Human Cancer Cells by Nahuoic Acid A

The Journal of Organic Chemistry
David E WilliamsRaymond J Andersen

Abstract

Nahuoic acids A-E (1-5) have been isolated from laboratory cultures of a Streptomyces sp. obtained from a tropical marine sediment. The structures of the new polyketides 2-5 were elucidated by analysis of spectroscopic data of the natural products and the chemical derivatives 6 and 7. Nahuoic acids 1-5 are in vitro inhibitors of the histone methyltransferase SETD8, and nahuoic acid A (1) and its pentaacetate derivative 8 inhibit the proliferation of several cancer cells lines in vitro with modest potency. At the IC50 for cancer cell proliferation, nahuoic acid A (1) showed selective inhibition of SETD8 in U2OS osteosarcoma cells that reflect its selectivity against a panel of pure histone methyl transferases. A cell cycle analysis revealed that the cellular toxicity of nahuoic acid A (1) is likely linked to its ability to inhibit SETD8 activity.

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Citations

Oct 1, 2016·Clinical Epigenetics·Ciro MiliteGianluca Sbardella
Mar 25, 2017·Chemical Reviews·H Ümit KaniskanJian Jin
Jan 18, 2018·Natural Product Reports·John W BluntMichèle R Prinsep
Jul 15, 2016·ChemMedChem·Ciro MiliteGianluca Sbardella
Dec 12, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Santiago LascanoPaola B Arimondo
Jan 26, 2020·Current Opinion in Chemical Biology·Laia Richart, Raphaël Margueron
Apr 10, 2020·Accounts of Chemical Research·Yifan Deng, Amos B Smith
Sep 22, 2017·Journal of the American Chemical Society·Qi LiuAmos B Smith

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