title: Design, Synthesis and Evaluation of Indene Derivatives as Retinoic Acid Receptor α Agonists.
abstract: A series of novel indene-derived retinoic acid receptor α (RARα) agonists have been designed and synthesized. The use of receptor binding, cell proliferation and cell differentiation assays demonstrated that most of these compounds exhibited moderate RARα binding activity and potent antiproliferative activity. In particular, 4-((3-isopropoxy-2,3-dihydro-1H-inden-5-yl)-carbamoyl)benzoic acid (36d), which showed a moderate binding affinity, exhibited a great potential to induce the differentiation of NB4 cells (68.88% at 5 μM). Importantly, our work established indene as a promising skeleton for the development of novel RARα agonists.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. guanx082@umn.edu.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Guan
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. peihualuo@zju.edu.cn.
authors.forename: Peihua
authors.initials: P
authors.lastname: Luo
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. qiaojunhe@zju.edu.cn.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. huyz@zju.edu.cn.
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. yybb@zju.edu.cn.
authors.forename: Huazhou
authors.initials: H
authors.lastname: Ying
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D011485:Protein Binding; D000072482:Retinoic Acid Receptor alpha / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D007192:Indenes; D000072482:Retinoic Acid Receptor alpha
keywords: agonist; all-trans-retinoic acid derivative; indene; retinoic acid receptor; structure and activity relationship