https://scholars.lib.ntu.edu.tw/handle/123456789/565274
Title: | 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity | Authors: | Lee H.-Y. Lee J.-F. Kumar S. Wu Y.-W. HuangFu W.-C. Lai M.-J. Li Y.-H. Huang H.-L. Kuo F.-C. Hsiao C.-J. Cheng C.-C. CHIA-RON YANG Liou J.-P. |
Keywords: | 3-Aroylindoles; Anticancer agents; Histone deacetylase inhibitors; Tubulin polymerization inhibition | Issue Date: | 2017 | Journal Volume: | 125 | Start page/Pages: | 1268-1278 | Source: | European Journal of Medicinal Chemistry | Abstract: | A series of 3-aroylindole hydroxamic acids (10–17) were developed based on the concept of a structural combination of tubulin and histone deacetylase (HDAC) inhibitors. This was accomplished by introducing hydroxamic acid-containing moieties at the N1 position of the tubulin assembly inhibitor, compound 9 (SCB01A, BPR0L075, phase II trial). Most of synthetic compounds produced in this way displayed comparable HDAC inhibitory activity, and four (10, 12–14) of them also inhibit tubulin assembly. Notably, compound 12 possesses not only tubulin and HDAC inhibitory activity but also shows HDAC6 selectivity over other HDAC isoforms. In addition, it exhibits remarkable inhibitory activity against the growth cancer cells in?vitro and in?vivo (PC3 and RPMI-8226?cells). Notably, it suppresses the growth of multiple myeloma xenografts without leading to the death of teated animals like reference compound. In sum, this study provided potential compounds with safer profiles for cancer treatment. ? 2016 Elsevier Masson SAS |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84996524189&doi=10.1016%2fj.ejmech.2016.11.033&partnerID=40&md5=203d00b2da8be27f9915cb5ff53f7b00 https://scholars.lib.ntu.edu.tw/handle/123456789/565274 |
ISSN: | 2235234 | DOI: | 10.1016/j.ejmech.2016.11.033 | SDG/Keyword: | 3 aroylindole derivative; histone deacetylase inhibitor; hydroxamic acid derivative; indole derivative; n (2 aminophenyl) 4 [6 methoxy 3 (3,4,5 trimethoxybenzoyl)indol 1 ylmethyl]benzamide; n hydroxy 3 [3 [6 methoxy 3 (3,4,5 trimethoxybenzoyl) 1h indol 1 ylsulfonyl]phenyl]acrylamide; n hydroxy 3 [4 [[6 methoxy 3 (3,4,5 trimethoxybenzoyl) 1h indol 1 yl]methyl]phenyl]acrylamide; n hydroxy 4 [ [6 methoxy 3 (3,4,5 trimetoxybenzoyl) 1h indol 1 yl]methyl]benzamide; unclassified drug; antineoplastic agent; HDAC6 protein, human; histone deacetylase; histone deacetylase inhibitor; hydroxamic acid; indole derivative; tubulin; tubulin modulator; animal experiment; animal model; antineoplastic activity; antiproliferative activity; Article; controlled study; drug structure; enzyme inhibition; growth inhibition; human; human cell; in vitro study; in vivo study; male; mouse; nonhuman; protein assembly; structure activity relation; animal; chemistry; drug design; drug effects; HeLa cell line; metabolism; nude mouse; pathology; prostate; Prostatic Neoplasms; tumor cell line; Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Design; HeLa Cells; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Hydroxamic Acids; Indoles; Male; Mice, Nude; Prostate; Prostatic Neoplasms; Tubulin; Tubulin Modulators |
Appears in Collections: | 藥學系 |
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