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.

[1]  N. Nakayama,et al.  Structures of nine oxygenated 4-methylene sterols from Hachijo marine sponge Theonella swinhoei , 1995, Steroids.

[2]  Hua Tang,et al.  Sinularosides A and B, bioactive 9,11-secosteroidal glycosides from the South China Sea soft coral Sinularia humilis Ofwegen. , 2012, Journal of natural products.

[3]  C. Djerassi,et al.  Sterols in marine invertebrates. 22. Isolation and structure elucidation of conicasterol and theonellasterol, two new 4-methylene sterols from the Red Sea sponges Theonella conica and Theonella swinhoei , 1981 .

[4]  H. Flack,et al.  On enantiomorph‐polarity estimation , 1983 .

[5]  H. Haisma,et al.  Histone acetyl transferases as emerging drug targets. , 2009, Drug discovery today.

[6]  G. Bifulco,et al.  Theonellasterols and conicasterols from Theonella swinhoei. Novel marine natural ligands for human nuclear receptors. , 2011, Journal of medicinal chemistry.

[7]  J. Seco,et al.  The assignment of absolute configuration by NMR , 2004 .

[8]  S. Arihara,et al.  Swinhosterols A−C, 4-Methylene Secosteroids from the Marine Sponge Theonella swinhoei , 1997 .

[9]  A. Mándi,et al.  Structure, absolute configuration, and conformational study of 12-membered macrolides from the fungus Dendrodochium sp. associated with the sea cucumber Holothuria nobilis Selenka. , 2013, The Journal of organic chemistry.

[10]  A. Zampella,et al.  Isoswinholide B and swinholide K, potently cytotoxic dimeric macrolides from Theonella swinhoei. , 2013, Bioorganic & medicinal chemistry.

[11]  Hua Tang,et al.  Steroids glycosylated with both D- and L-arabinoses from the South China Sea gorgonian Dichotella gemmacea. , 2013, Journal of natural products.

[12]  D. Doddrell,et al.  Pyridine-induced solvent shifts in the nuclear magnetic resonance spectra of hydroxylic compounds , 1968 .

[13]  S. Berger,et al.  Histone modifications in transcriptional regulation. , 2002, Current opinion in genetics & development.

[14]  Gianluigi Lauro,et al.  Inverse virtual screening of antitumor targets: pilot study on a small database of natural bioactive compounds. , 2011, Journal of natural products.

[15]  P. Cole,et al.  Synthesis and evaluation of a potent and selective cell-permeable p300 histone acetyltransferase inhibitor. , 2005, Journal of the American Chemical Society.

[16]  R. Goodman,et al.  CBP/p300 in cell growth, transformation, and development. , 2000, Genes & development.

[17]  A. Mándi,et al.  Herbarone, a rearranged heptaketide derivative from the sea hare associated fungus Torula herbarum. , 2012, Journal of natural products.

[18]  J. Su,et al.  4-Methylenesterols from a Sponge Theonella swinhoei , 2012, Marine drugs.

[19]  A. Mcinnes,et al.  Identification of C-24 alkyl epimers of marine sterols by 13C nuclear magnetic resonance spectroscopy , 1978 .

[20]  G. Bifulco,et al.  Discovery and synthesis of namalide reveals a new anabaenopeptin scaffold and peptidase inhibitor. , 2012, Journal of medicinal chemistry.

[21]  E. Fattorusso,et al.  Steroids from sponges: Recent reports , 1999, Steroids.

[22]  D. Musumeci,et al.  Secosteroids of marine origin , 2004, Steroids.