Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase.
Four novel bisulfide bromotyrosine derivatives, psammaplins E (9), F (10), G (11), and H (12), and two new bromotyrosine derivatives, psammaplins I (13) and J (14), were isolated from the sponge Pseudoceratina purpurea, along with known psammaplins A (4), B (6), C (7), and D (8) and bisaprasin (5). The structures of psammaplins E (9) and F (10), which each contain an oxalyl group rarely found in marine organisms, were determined by spectroscopic analysis. Compounds 4, 5, and 10 are potent histone deacetylase inhibitors and also show mild cytotoxicity. Furthermore, compounds 4, 5, and 11 are potent DNA methyltransferase inhibitors. The biogenetic pathway previously proposed for the psammaplins class is also revisited.
Department of Chemistry and Biochemistry & Institute of Marine Sciences, University of California, Santa Cruz 95064, USA.
Ivette C
IC
Piña
Jeffrey T
JT
Gautschi
Gui-Yang-Sheng
GY
Wang
Miranda L
ML
Sanders
Francis J
FJ
Schmitz
Dennis
D
France
Susan
S
Cornell-Kennon
Lidia C
LC
Sambucetti
Stacy W
SW
Remiszewski
Larry B
LB
Perez
Kenneth W
KW
Bair
Phillip
P
Crews
D000818:Animals; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D004220:Disulfides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D011161:Porifera / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D004220:Disulfides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D013463:Sulfuric Acid Esters; C407994:bisaprasin 11'-sulfate; C098378:psammaplin A; D014443:Tyrosine; D015254:DNA Modification Methylases