biostudies-literatureMehndiratta SMinistry of Science and Technology, Taiwan74-84https://www.ebi.ac.uk/biostudies/studies/S-EPMC7655065biostudies-literatureUnknown36(1)A series of 3-subsituted quinolinehydroxamic acids has been synthesised and evaluated for their effect on human lung cancer cell line (A549), human colorectal cancer cell line (HCT116) and HDAC isoforms 1, 2, 6, and 8. The results indicated that substitution at C3 of quinoline is favoured for HDAC6 selectivity. Two compounds (<b>25</b> and <b>26</b>) were also found to be potent anti-proliferative compounds with IC₅₀ values ranging from 1.29 to 2.13 µM against A549 and HCT116 cells. These compounds displayed remarkable selectivity for HDAC6 over other HDAC isoforms with nanomolar IC₅₀ values. Western blot analysis revealed that compounds of this series activate apoptotic caspase pathway as indicated by cleavage of caspase 3, 8, and 9 and also increase phosphorylated HJournal of enzyme inhibition and medicinal chemistryEffect of 3-subsitution of quinolinehydroxamic acids on selectivity of histone deacetylase isoforms.PMC7655065MOST108-2320-B-038–042-MY3Mehndiratta SChen MCLee CHLee HYLiou JPLai MJChao YHfalseEffect of 3-subsitution of quinolinehydroxamic acids on selectivity of histone deacetylase isoforms.A series of 3-subsituted quinolinehydroxamic acids has been synthesised and evaluated for their effect on human lung cancer cell line (A549), human colorectal cancer cell line (HCT116) and HDAC isoforms 1, 2, 6, and 8. The results indicated that substitution at C3 of quinoline is favoured for HDAC6 selectivity. Two compounds (<b>25</b> and <b>26</b>) were also found to be potent anti-proliferative compounds with IC₅₀ values ranging from 1.29 to 2.13 µM against A549 and HCT116 cells. These compounds displayed remarkable selectivity for HDAC6 over other HDAC isoforms with nanomolar IC₅₀ values. Western blot analysis revealed that compounds of this series activate apoptotic caspase pathway as indicated by cleavage of caspase 3, 8, and 9 and also increase phosphorylated H2021-01-01T00:00:00Z2021 Dec2026-04-30T16:00:00.87Z2021-02-19T18:07:55ZS-EPMC76550653316179910.1080/14756366.2020.1839446