1383447-50-4Relevant academic research and scientific papers
Psammaplin A derivative as well as preparation method and application thereof
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, (2021/04/21)
The invention provides a Psammaplin A derivative as well as a preparation method and application thereof, and belongs to the field of medicinal chemistry, wherein the Psammaplin A derivative has a structural formula represented by a formula (I), wherein in the formula, R1, R2, R3, R4, R5 and R6 are respectively selected from any one of H, OH, OCH3, Br, 3,5-di-fluoro-benzyloxy, 2-fluoro-benzyloxy, 3-fluoro-benzyloxy, 4-cyano-benzyloxy and 4-trifluoromethyl-benzyloxy; R1 and R4 are the same or different, R2 and R5 are the same or different, and R3 and R6 are the same or different. According to the invention, a new structure and thought are provided for the design of a novel HDAC inhibitor, and the developed Psammaplin A derivative has a good anti-tumor cytotoxicity effect, and also provides an important theoretical reference for the development of HDAC-based anti-tumor drugs.
Fluorescent analogs of the marine natural product psammaplin A: Synthesis and biological activity
Hentschel, Fabia,Sasse, Florenz,Lindel, Thomas
supporting information; experimental part, p. 7120 - 7133 (2012/09/22)
The symmetrical disulfide psammaplin A from the marine sponge Pseudoceratina sp. was synthesized and structurally altered by replacement of one of the α-(hydroxyimino)acyl units by a fluorescent 4-coumarinacetyl moiety. Thus, the first fluorescent analogs of psammaplin A were obtained. Structural variation also covered the substitution pattern of the phenyl ring. Cytotoxicity of psammaplin A against the mouse fibroblast cell line L-929 (IC50 0.42 μg mL-1) was about two-fold higher than that of the fluorescent hybrid compounds, whereas the disulfide containing two 4-coumarinacetyl moieties was inactive. Fluorescence microscopy revealed uptake of the 4-coumarinacetyl-α-(hydroxyimino)acyl hybrids into the cytoplasm leading to fluorescence in close proximity of the nuclear envelope, most likely in the Golgi apparatus. We did not observe strong fluorescence inside the nucleus, where most of the target histone deacetylases are located. We conclude that reduction of the disulfide probably takes place outside the nucleus. The psammaplin-derived thiol exhibited potent activity against histone deacetylase in the low nanomolar range, but diminished cytotoxicity. Antimicrobial activity of the new derivatives was also determined.
