Hydroxamates of para-aminobenzoic acid as selective inhibitors of HDAC8.
Fiche publication
Date publication
décembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Kulandaivelu U, Chilakamari LM, Jadav SS, Rao TR, Jayaveera KN, Shireesha B, Hauser AT, Senger J, Marek M, Romier C, Jung M, Jayaprakash V
Lien Pubmed
Résumé
A series of hydroxamates (4a-4l) were prepared from p-aminobenzoic acid to inhibit HDAC8. The idea is to substitute rigid aromatic ring in place of less rigid piperazine ring of hydroxamates reported earlier by our group. It is expected to increase potency retaining the selectivity. Result obtained suggested that the modifications carried out retained the selectivity towards HDAC8 isoform and increasing the potency in very few cases. Increase in potency is also associated with variation in cap aryl region. Two compounds (4f &4l) were found to inhibit HDAC8 at concentrations (IC50) less than 20muM.
Référence
Bioorg Chem. 2014 Dec;57:116-20