Bastadin 20 and bastadin O-sulfate esters from Ianthella basta: novel modulators of the Ry1R FKBP12 receptor complex.
New compounds bastadin 20 (9), 15,34-O-disulfatobastadin 7 (10), and 10-O-sulfatobastadin 3 (11) were isolated from Ianthella basta collected in Exmouth Gulf, Western Australia. Compounds 10 and 11 exhibited moderate differential activity as SR Ca2+ channel agonists (EC50 13.6 and 100 microM, respectively) of the Ry1R FKBP12 complex, while the potency of 9 was almost half that of 10 (EC50 20.6 microM). The problem of dereplication of bastadins was addressed using 1H-NMR "fingerprinting" of MeO signals in the corresponding permethyl bastadin derivatives.
Franklin
M A
MA
Department of Chemistry, University of California, Davis 95616, USA.
Penn
S G
SG
Lebrilla
C B
CB
Lam
T H
TH
Pessah
I N
IN
Molinski
T F
TF
D000818:Animals; D002120:Calcium Channel Agonists / Q000737:chemistry* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D055768:Halogenated Diphenyl Ethers; D009682:Magnetic Resonance Spectroscopy; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D010647:Phenyl Ethers / Q000737:chemistry* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D019837:Ryanodine Receptor Calcium Release Channel; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C103978:10-O-sulfatobastadin 3; C103977:15,34-O-disulfatobastadin 7; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D055768:Halogenated Diphenyl Ethers; D009124:Muscle Proteins; D010456:Peptides, Cyclic; D010647:Phenyl Ethers; D019837:Ryanodine Receptor Calcium Release Channel; C103976:bastadin 20