Williams David E, Izard Fanny, Arnould Stéphanie, Dalisay Doralyn S, Tantapakul Cholpisut, Maneerat Wisanu, Matainaho Teatulohi, Julien Eric, Andersen Raymond J
Departments of Chemistry and Earth, Ocean and Atmospheric Sciences, University of British Columbia , 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier (ICM) , Montpellier F-34298, France.
J Org Chem. 2016 Feb 19;81(4):1324-32. doi: 10.1021/acs.joc.5b02569. Epub 2016 Feb 1.
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.
纳霍酸A - E（1 - 5）是从一株从热带海洋沉积物中获得的链霉菌属的实验室培养物中分离得到的。新聚酮化合物2 - 5的结构通过对天然产物及其化学衍生物6和7的光谱数据分析得以阐明。纳霍酸1 - 5是组蛋白甲基转移酶SETD8的体外抑制剂，纳霍酸A（1）及其五乙酸酯衍生物8在体外以适度的效力抑制几种癌细胞系的增殖。在癌细胞增殖的IC50浓度下，纳霍酸A（1）在U2OS骨肉瘤细胞中显示出对SETD8的选择性抑制，这反映了其对一组纯组蛋白甲基转移酶的选择性。细胞周期分析表明，纳霍酸A（1）的细胞毒性可能与其抑制SETD8活性的能力有关。
