Aaptamine, an alkaloid from the sponge Aaptos suberitoides, functions as a proteasome inhibitor.
Aaptamine (1), isoaaptamine (2), and demethylaaptamine (3) were isolated from the marine sponge Aaptossuberitoides collected in Indonesia as inhibitors of the proteasome. They inhibited the chymotrypsin-like and caspase-like activities of the proteasome with IC(50) values of 1.6-4.6 microg/mL, while they showed less inhibition of the trypsin-like activity of the proteasome. The three compounds showed cytotoxic activities against HeLa cells, but their cytotoxicity did not correlate with their potency as proteasome inhibitors, strongly suggesting that their proteasomal inhibitory activity is dispensable to their cytotoxicity.
Tsukamoto
Sachiko
S
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan. sachiko@kumamoto-u.ac.jp
Yamanokuchi
Rumi
R
Yoshitomi
Makiko
M
Sato
Kohei
K
Ikeda
Tsuyoshi
T
Rotinsulu
Henki
H
Mangindaan
Remy E P
RE
de Voogd
Nicole J
NJ
van Soest
Rob W M
RW
Yokosawa
Hideyoshi
H
D000818:Animals; D006367:HeLa Cells; D006801:Humans; D009287:Naphthyridines / Q000302:isolation & purification / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D061988:Proteasome Inhibitors
D009287:Naphthyridines; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; C043986:aaptamine