Abstract
Some N-phenyl lipoamide and 8-mercapto-N-phenyloctanamide derivatives were synthesized and their in vitro antiproliferative activity was evaluated. The experimental results indicated that 8-mercapto-N-phenyloctanamides might be good histone deacetylase inhibitors rather than N-phenyl lipoamides, who had thiol moiety at C6 position. To verify the antiproliferation data on structural basis, in silico docking studies of the representative compounds into the crystal structure of histone deacetylase-like protein using AutoDock 4.0 program were performed. Furthermore, sulfur acetylated 8-mercapto-N-phenyloctanamide improved its in vitro antiproliferative activity, probably due to the increasing of its cell membrane permeability. While the identification of enzymatic target of N-phenyl lipoamides with dithiolane is still ongoing.
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Acknowledgments
The authors are thankful to Hangzhou Minsheng Pharmaceutical Group Co., Ltd. for antiproliferative evaluation. Partial financial support from Hangzhou Minsheng Pharmaceutical Group Co., Ltd. are also gratefully acknowledged.
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The authors declare that they have no conflict of interest regarding the work reported in this manuscript.
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Zhang, SJ., Hu, WX. Synthesis, antiproliferation, and docking studies of N-phenyl-lipoamide and 8-mercapto-N-phenyloctanamide derivatives: effects of C6 position thiol moiety. Med Chem Res 21, 3312–3320 (2012). https://doi.org/10.1007/s00044-011-9879-7
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DOI: https://doi.org/10.1007/s00044-011-9879-7