Hyrtioreticulins A-E, indole alkaloids inhibiting the ubiquitin-activating enzyme, from the marine sponge Hyrtios reticulatus.
Hyrtioreticulins A-E (1-5) were isolated from the marine sponge Hyrtios reticulatus, along with a known alkaloid, hyrtioerectine B (6). Structural elucidation on the basis of spectral data showed that 1, 2, and 5 are new tetrahydro-β-carboline alkaloids, while 3 and 4 are new azepinoindole-type alkaloids. Hyrtioreticulins A and B (1 and 2) inhibited ubiquitin-activating enzyme (E1) with IC(50) values of 0.75 and 11μg/mL, respectively, measured by their inhibitory abilities against the formation of an E1-ubiquitin intermediate. So far, only five E1 inhibitors, panapophenanthrine, himeic acid A, largazole, and hyrtioreticulins A and B (1 and 2), have been isolated from natural sources and, among them, 1 is the most potent E1 inhibitor.
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Rumi
R
Yamanokuchi
Kumiko
K
Imada
Mitsue
M
Miyazaki
Hikaru
H
Kato
Tadashi
T
Watanabe
Masahiro
M
Fujimuro
Yasushi
Y
Saeki
Sosuke
S
Yoshinaga
Hiroaki
H
Terasawa
Noriyuki
N
Iwasaki
Henki
H
Rotinsulu
Fitje
F
Losung
Remy E P
RE
Mangindaan
Michio
M
Namikoshi
Nicole J
NJ
de Voogd
Hideyoshi
H
Yokosawa
Sachiko
S
Tsukamoto
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D026121:Indole Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C505316:hyrtioerectine B; D044764:Ubiquitin-Activating Enzymes