Design, Synthesis and Biological Evaluation of New HDAC1 and HDAC2 Inhibitors Endowed with Ligustrazine as a Novel Cap Moiety.
Mohammad M Al-SaneaLizaveta GotinaMamdouh Fa MohamedDella Grace Thomas ParambiHesham A M GomaaBijo MathewBahaa G M YoussifKhalid Saad AlharbiZainab M ElsayedMohamed Abdelwahab AbdelgawadWagdy M EldehnaPublished in: Drug design, development and therapy (2020)
Compound 7a was found to be the most potent analog in this study toward HDAC1 and HDAC2 with IC50 values equal 114.3 and 53.7 nM, respectively. Moreover, it was the most effective counterpart (IC50 = 1.60 µM), with 4.7-fold enhanced efficiency than reference drug Gefitinib (IC50 = 7.63 µM) against SH-SY5Y cells. Whereas, compound 8a (IC50 = 1.96 µM) was the most active member toward HT-29 cells, being 2.5-times more potent than Gefitinib (IC50 = 4.99 µM). Collectively, these results suggest that 7a merits further optimization and development as an effective new HDACI lead compound.