In our efforts to discover novel HDAC6 selective inhibitors, we designed and synthesized a series of hydroxamic acid small molecules and evaluated their biological effects. Structure−activity and structure-selectivity relationship studies disclosed three novel HDAC6 inhibitors with excellent potency and selectivity. Compound 77 (HPOB), 123 (HPB) and 124 showed IC50 values of 56, 31, and 11 nM against HDAC6 enzyme with a selectivity ratio of 52, 36 and 25 respectively compared to HDAC1 enzyme. Our lead compounds HPOB and HPB causes growth inhibition of normal and transformed cells but does not induce cell death. These HDAC6-selective inhibitors shows potential candidacy for combination therapy to enhance the efficacy of certain anti-cancer drugs.

Design, synthesis and biological effects of novel HDAC6 selective inhibitors

253rd National Meeting (2017)

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