title: Novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides as histone deacetylase inhibitors and antitumor agents.
abstract: Histone deacetylases (HDAC) are currently a group of validated targets for anticancer drug discovery and development. In our research program to find novel small molecules targeting these enzymes, we designed and synthesized two series of 3-hydroxyimino-2-oxoindoline- and 3- methoxyimino-2-oxoindoline-based N-hydroxypropenamides (3a-g, 6a-g). The results show that these propenamides potently inhibited HDAC2 with IC50 values in sub-micromolar range, approximately 10-fold lower than that of SAHA (also known as suberoylanilohydroxamic acid). Evaluation of cytotoxicity of these compounds in three human cancer cell lines revealed that most of the synthesized compounds were up to 5-fold more cytotoxic than SAHA. Docking studies showed that the compounds bound to HDAC2 at the binding site with higher binding affinities compared to SAHA. Our present results demonstrate that these novel 3-substituted-2-oxoindoline-based N-hydroxypropenamides are potential for further development as anticancer agents.
authors.forename: Do T M
authors.initials: do TM
authors.lastname: Dung
authors.forename: Phan T P
authors.initials: PT
authors.lastname: Dung
authors.forename: Dao T K
authors.initials: DT
authors.lastname: Oanh
authors.forename: Pham T
authors.initials: PT
authors.lastname: Hai
authors.forename: Le T T
authors.initials: le TT
authors.lastname: Huong
authors.forename: Vu D
authors.initials: VD
authors.lastname: Loi
authors.forename: Hyunggu
authors.initials: H
authors.lastname: Hahn
authors.forename: Byung W
authors.initials: BW
authors.lastname: Han
authors.forename: Jisung
authors.initials: J
authors.lastname: Kim
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Vietnam. shan@chungbuk.ac.kr oanhdtk@hup.edu.vn shan@chungbuk.ac.kr.
authors.forename: Nguyen-Hai
authors.initials: NH
authors.lastname: Nam
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2