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

Autor: Teatulohi Matainaho, Doralyn S. Dalisay, Eric Julien, Cholpisut Tantapakul, David E. Williams, Stéphanie Arnould, Fanny Izard, Raymond J. Andersen, Wisanu Maneerat
Přispěvatelé: Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Rok vydání: 2016
Předmět:
0301 basic medicine
Geologic Sediments
MESH: Histone Methyltransferases
MESH: Streptomyces
MESH: Molecular Structure
Antineoplastic Agents
[SDV.CAN]Life Sciences [q-bio]/Cancer
01 natural sciences
Streptomyces
Cell Line
Histones
03 medical and health sciences
MESH: Cell Proliferation
Humans
IC50
MESH: Polyketides
Cell Proliferation
MESH: Histones
MESH: Humans
Molecular Structure
biology
010405 organic chemistry
Cell growth
Chemistry
Organic Chemistry
MESH: Histone-Lysine N-Methyltransferase
Histone-Lysine N-Methyltransferase
MESH: Geologic Sediments
biology.organism_classification
Molecular biology
In vitro
MESH: Cell Line
0104 chemical sciences
3. Good health
030104 developmental biology
Histone
Biochemistry
Cell culture
Polyketides
Histone methyltransferase
Cancer cell
Histone Methyltransferases
biology.protein
MESH: Antineoplastic Agents
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Journal of Organic Chemistry
Journal of Organic Chemistry, American Chemical Society, 2016, 81 (4), pp.1324-1332. ⟨10.1021/acs.joc.5b02569⟩
ISSN: 1520-6904
0022-3263
Popis: International audience; 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.
Databáze: OpenAIRE
Externí odkaz: