title: Design, synthesis and docking study of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as inhibitors of protein tyrosine phosphatase 1B.
abstract: A series of novel 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives was designed, and synthesized based on our previous studies. Also their activities were evaluated as competitive inhibitors of protein tyrosine phosphatase 1B (PTP1B). Compounds 6d-6g, 7b, 7c, 7e, 7j, 7k, 7m, 14b and 14e-14f showed potent inhibitory effects against PTP1B, and compound 7e, the most potent among the series, had an IC50 of 4.6 μM. Also a Surflex-Dock docking model of 7e was studied. Compound 7e showed a negative binding energy of -7.35 kcal/mol and a high affinity to PTP1B residues (Gly220, Ala217, Arg221, Asp181, Ser216, Cys215, Phe182, Gln262 and Ile219) in the active sites, indicating that it may stabilize the open form and generate tighter binding to the catalytic sites of PTP1B.
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Zengtao
authors: Z
authors: Wang
authors: School of Pharmacy, Wenzhou Medical College, 1210 University Town, Wenzhou, Zhejiang 325035, China; Wenzhou Undersun Biotechnology Co., Ltd, Wenzhou, Zhejiang, China.
authors: Zhiguo
authors: Z
authors: Liu
authors: KIST Gangneung Institute, Gangneung 210-340, Republic of Korea.
authors: Woojung
authors: W
authors: Lee
authors: KIST Gangneung Institute, Gangneung 210-340, Republic of Korea.
authors: Su-Nam
authors: SN
authors: Kim
authors: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors: Goo
authors: G
authors: Yoon
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: shcheon@chonnam.ac.kr.
authors: Seung Hoon
authors: SH
authors: Cheon
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Docking study; PTP1B; Synthesis; Thiazolidinediones