Nepali K1, Lee HY1, Lai MJ2, Ojha R1, Wu TY3, Wu GX1, Chen MC4, Liou JP5.
Eur J Med Chem. 2016 Dec 21;127:115-127. doi: 10.1016/j.ejmech.2016.12.039. [Epub ahead of print]This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5-18) were synthesized and structure-activity relationship studies indicated that the change of the tetrahydro-γ-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. Read More