title: Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors.
abstract: A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC50=1.18-8.01 μg/mL) and PTP1B (IC50=0.85-8.75 μg/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC50 values of 1.18 and 0.85 μg/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na3VO4 (IC50=0.93 μg/mL) and oleanolic acid (IC50=0.85 μg/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor.
authors.affiliation: College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China. Electronic address: chemlab.lnnu@163.com.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jin
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Gao
authors.affiliation: College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China.
authors.forename: Tongchuan
authors.initials: T
authors.lastname: Luo
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shao
authors.affiliation: National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jli@simm.ac.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D013830:Thiadiazoles; C517008:CDC25B protein, human; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D020687:cdc25 Phosphatases
keywords: Cancer; Cdc25B; PTP1B; Thiadiazole amides; Type-2 diabetes and obesity