Abstract
A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in vitro and in vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC50 1.28 nM and 1.34 nM) and HDAC 2 (IC50 0.90 and 0.53 nM). N-Hydroxy-3-{4-[2-(1H-indol-4-yl)-ethylsulfamoyl]-phenyl}-acrylamide (13) inhibited the human cancer cell growth of PC3, A549, MDA-MB-231 and AsPC-1 with a GI50 of 0.14, 0.25, 0.32, and 0.24 μM, respectively. In in vivo evaluations bearing prostate PC3 xenografts nude mice model, compound 13 suppressed tumor growth with a tumor growth inhibition (TGI) of 62.2%. Immunohistochemistry of protein expressions, in PC-3 xenograft model indicated elevated acetyl-histone 3 and prominently inhibited HDAC2 protein expressions. Therefore, compound 13 could be a suitable lead for further investigation and the development of selective HDAC 2 inhibitors as potent anti-cancer compounds.
Original language | English |
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Pages (from-to) | 13-23 |
Number of pages | 11 |
Journal | European Journal of Medicinal Chemistry |
Volume | 134 |
DOIs | |
Publication status | Published - Jul 7 2017 |
Keywords
- Acrylamide
- Cancer
- HDAC
- Hydroxamic acid
- Indole
- Prostate cancer
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry