Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity.

Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity. Eur J Pharm Sci. 2019 Aug 14;:105046 Authors: Trivedi P, Adhikari N, Amin SA, Bobde Y, Ganesh R, Jha T, Ghosh B Abstract HDAC8 has been established as one of the vital targets as far as the cancer is concerned. Different compounds having potential HDAC inhibitory activity have been approved by USFDA. However, none of these compounds are selective towards specific HDAC isoform. In this current study, some new hydroxamate derivatives with alkylpiperidine and alkylpiperazine linker moieties have been designed, synthesized and biologically evaluated. All these compounds are effective HDAC8 inhibitors comprising more or less similar cytotoxic potential against different cancer cell lines. It is observed that the piperazine scaffold containing compound is more active than the compound with piperidine scaffold for exerting HDAC8 inhibitory activity. Moreover, the 4-quinolyl cap group is better than the biphenyl group which is better than the benzyl group for producing higher HDAC8 inhibition as well as cytotoxicity. These compounds displayed selective HDAC8 inhibition over HDAC3. Moreover, these compounds showed an increased caspase3/7 activity suggesting their anticancer potential through modulation of apoptotic pathways. Molecular docking stud...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research