New steroids with a rearranged skeleton as (h)P300 inhibitors from the sponge Theonella swinhoei.
Swinhoeisterols A (1) and B (2), two novel sterols with an unprecedented 6/6/5/7 ring system, were isolated from the sponge Theonella swinhoei. The structures and absolute configurations were elucidated by spectroscopic analysis, X-ray single-crystal diffraction, modified Mosher's method, and TDDFT/ECD calculations. The cytotoxicity of these compounds toward A549 and MG-63 cells encourages studies on their potential target using an inverse virtual screening approach. The predicted inhibitor of h(p300) was corroborated by an in vitro biological test.
Research Center for Marine Drugs, and Department of Pharmacology, School of Pharmacy, Second Military Medical University , 325 Guo-He Road, Shanghai 200433, P. R. China.
Jun
J
Gong
Peng
P
Sun
Nan
N
Jiang
Raffaele
R
Riccio
Gianluigi
G
Lauro
Giuseppe
G
Bifulco
Tie-Jun
TJ
Li
William H
WH
Gerwick
Wen
W
Zhang
D000818:Animals; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors*; D006801:Humans; D008386:Marine Biology; D008968:Molecular Conformation; D015394:Molecular Structure; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D047232:Theonella / Q000737:chemistry*
D013256:Steroids; C000590011:swinhoeisterol A; C000590012:swinhoeisterol B; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human