title: Synthesis, biological evaluation and molecular docking studies of novel 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives.
abstract: In present study, a series of new 2-(1,3,4-oxadiazol-2-ylthio)-1-phenylethanone derivatives (6a-6x) as potential focal adhesion kinase (FAK) inhibitors were synthesized. The bioassay assays demonstrated that compound 6i showed the most potent activity, which inhibited the growth of MCF-7 and A431 cell lines with IC(50) values of 140 ± 10 nM and 10 ± 1 nM, respectively. Compound 6i also exhibited significant FAK inhibitory activity (IC(50)=20 ± 1 nM). Docking simulation was performed to position compound 6i into the active site of FAK to determine the probable binding model.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Zhang
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Yin
authors.initials: Y
authors.lastname: Luo
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Gong
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000098:Acetophenones / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020134:Catalytic Domain; D002417:Cattle; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000098:Acetophenones; D047428:Protein Kinase Inhibitors; D051416:Focal Adhesion Protein-Tyrosine Kinases