Exploration of novel 5′(7′)-substituted-2′-oxospiro[1,3]dioxolane-2,3′-indoline-based N-hydroxypropenamides as histone deacetylase inhibitors and antitumor agents

A series of novel 5′(7′)-substituted-2′-oxospiro[1,3]dioxolane-2,3′-indoline-based N-hydroxypropenamides were designed, synthesized and evaluated for histone deacetylase (HDAC) inhibition and cytotoxicity. It was found that the compounds in this series displayed potent inhibitory effects against HDA...

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Published inArabian journal of chemistry Vol. 10; no. 4; pp. 465 - 472
Main Authors Dung, Do Thi Mai, Dung, Phan Thi Phuong, Oanh, Dao Thi Kim, Vu, Tran Khac, Hahn, Hyunggu, Han, Byung Woo, Pyo, Minji, Kim, Young Guk, Han, Sang-Bae, Nam, Nguyen-Hai
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.05.2017
Subjects
Dioxolane
Histone deacetylase
Hydroxamic acid
Indoline
N-hydroxypropenamide
Hydroxamic acid
Histone deacetylase
Indoline
N-hydroxypropenamide
Dioxolane
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Summary:A series of novel 5′(7′)-substituted-2′-oxospiro[1,3]dioxolane-2,3′-indoline-based N-hydroxypropenamides were designed, synthesized and evaluated for histone deacetylase (HDAC) inhibition and cytotoxicity. It was found that the compounds in this series displayed potent inhibitory effects against HDAC2 with IC50 values as low as 0.284μM, almost comparable to that of SAHA (IC50, 0.265μM), a positive control. In Western blot analysis, these compounds also exhibited noted inhibition toward histone deacetylation and this inhibition was found to correlate well with the cytotoxicity of the compounds in three human cancer cell lines. Docking studies indicated the compounds in this series bound to HDAC2 with high binding affinities (∼−9.8kcal/mol) compared to SAHA (−7.4kcal/mol).
ISSN:1878-5352
1878-5379
DOI:10.1016/j.arabjc.2015.10.007