title: Synthesis of the novel elemonic acid derivatives as Pin1 inhibitors.
abstract: A novel series of elemonic acid derivatives were synthesized and evaluated for their inhibitory activity on Pin1. Five compounds displayed significantly improved ability to inhibit Pin1 activity at micromolar levels. Compound 10 with 2-carboxylmethylene was the most active one with an IC50 value of 0.57 μM. The docking models of Pin1 support that introduction of an acidic group to elemonic acid enhance the Pin1 inhibitory activity.
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Qingtong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. Electronic address: yongkui.jing@mssm.edu.
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: linxiang.zhao@vip.sina.com.
authors.forename: Linxiang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: C432163:3-oxo-tirucall-8,24-dien-21-oic acid; D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D014315:Triterpenes; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: Anticancer; Elemonic acid; Pin1 inhibition; Tirucallane; Triterpenoid