title: 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.
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.
authors.affiliation: Departments of Chemistry and Earth, Ocean and Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier (ICM) , Montpellier F-34298, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Izard
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier (ICM) , Montpellier F-34298, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Arnould
authors.affiliation: Departments of Chemistry and Earth, Ocean and Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Doralyn S
authors.initials: DS
authors.lastname: Dalisay
authors.affiliation: Departments of Chemistry and Earth, Ocean and Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Cholpisut
authors.initials: C
authors.lastname: Tantapakul
authors.affiliation: Departments of Chemistry and Earth, Ocean and Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Wisanu
authors.initials: W
authors.lastname: Maneerat
authors.affiliation: University of Papua New Guinea , Port Moresby 121, Papua New Guinea.
authors.forename: Teatulohi
authors.initials: T
authors.lastname: Matainaho
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier (ICM) , Montpellier F-34298, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Julien
authors.affiliation: Departments of Chemistry and Earth, Ocean and Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Andersen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D019015:Geologic Sediments; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006657:Histones / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D061065:Polyketides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D061065:Polyketides; C580730:nahuoic acid A; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase