Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1)


Tasdemir D., Mallon R., Greenstein M., Feldberg L., Kim S., Collins K., ...Daha Fazla

JOURNAL OF MEDICINAL CHEMISTRY, cilt.45, ss.529-532, 2002 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 45 Konu: 2
  • Basım Tarihi: 2002
  • Doi Numarası: 10.1021/jm0102856
  • Dergi Adı: JOURNAL OF MEDICINAL CHEMISTRY
  • Sayfa Sayıları: ss.529-532

Özet

Raf/MEK-1/MAPK cascade inhibitor activity-directed fractionation of the sponge Stylissa massa afforded eight known alkaloids: aldisine (1), 2-bromoaldisine (2), 10Z-debromohymenialdisine (3), 10E-hymenialdisine (4), 10Z-hymenialdisine (5), hymenin (6), oroidin (7), and 4,5-dibromopyrrole-2-carbonamide (8). Both 4 and 5 showed significant enzyme inhibitory activity (IC50 3 and 6 nM, respectively). Secondary assays identified these compounds as potent MEK-1 inhibitors. Compounds 4 and 5 also inhibited the growth of human tumor LoVo cells.