title: Synthesis and biological evaluation of 7-azaisoindigo derivatives.
abstract: A series of novel 7-azaisoindigo derivatives 3-14 were designed, synthesized, and structurally characterized by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analyses. Their antiproliferative activities were evaluated in a hormone-independent prostate cancer cell line DU145. Among them, compounds 8, 9, 14 showed the highest activities. Our study also showed that compounds 7, 11, 12 exhibited higher inhibitory activities on CDK2/cyclin A than that of the positive control meisoindigo. Western blot analysis on DU145 cells treated with compounds 7 and 9 demonstrated that 7-azaisoindigo derivatives could decrease the level of CDK2 activity (phosphorylation) and the expression of cyclin D1, and increase the expression of endogenous cyclin-dependent inhibitor p27.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Shi-Ning
authors.initials: SN
authors.lastname: Yao
authors.forename: Jing-cai
authors.initials: JC
authors.lastname: Chen
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Hua
authors.forename: Qi-Zheng
authors.initials: QZ
authors.lastname: Yao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D013329:Structure-Activity Relationship
chemical_list: D019925:Cyclin A; D007211:Indoles; C529858:azaisoindigo; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2