Structure-based design generated novel hydroxamic acid based preferential HDAC6 lead inhibitor with on-target cytotoxic activity against primary choroid plexus carcinoma.

ABSTRACT: Histone deacetylase 6 (HDAC6) is an attractive target for cancer therapeutic intervention. Selective HDAC6 inhibitors is important to minimise the side effects of pan inhibition. Thus, new class of hydroxamic acid-based derivatives were designed on structural basis to perform preferential activity against HDAC6 targeting solid tumours. Interestingly, 1-benzylbenzimidazole-2-thio-N-hydroxybutanamide 10a showed impressive preference with submicromolar potency against HDAC6 (IC₅₀ = 510 nM). 10a showed cytotoxic activity with interesting profile against CCHE-45 at (IC₅₀ = 112.76 µM) when compared to standard inhibitor Tubacin (IC₅₀ = 20 µM). Western blot analysis of acetylated-α-tubulin verified the HDAC6 inhibiting activity of 10a. Moreover, the insignificant

SUBMITTER: Kassab SE 

PROVIDER: S-EPMC6522981 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature