New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation.
New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.
Imperial College London, South Kensington Campus, Department of Chemistry, London, UK SW7 2AZ.
Matthias G J
MG
Baud
Thomas
T
Leiser
Franz-Josef
FJ
Meyer-Almes
Matthew J
MJ
Fuchter
D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D004220:Disulfides / Q000138:chemical synthesis* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010081:Oxazolone / Q000737:chemistry; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D001688:Biological Products; D004220:Disulfides; D056572:Histone Deacetylase Inhibitors; C098378:psammaplin A; D010081:Oxazolone; D014443:Tyrosine; D006655:Histone Deacetylases