title: Design, synthesis and biological evaluation of [1,2,3]triazolo[4,5-d]pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents.
abstract: A series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives bearing a hydrazone moiety were designed, synthesized and evaluated for their antiproliferative activity against several cancer cell lines of different origins by MTT assay. Most of the synthesized compounds demonstrated moderate to good activity against the cancer cell lines selected. Especially, compound 43 showed the most potent antiproliferative activity as well as good selectivity between cancer and normal cells (IC50values of 0.85 μM against MGC-803 and 56.17 μM against GES-1). In addition, compound 43 evidently inhibited the colony formation of MGC-803 cells at 0.8 μM. Further mechanism studies revealed that compound 43 could induce apoptosis of MGC-803 cells probably through the mitochondrial pathway accompanied with decrease of the mitochondrial membrane potential (MMP), activations of caspase-9/3, up-regulation of the expression of Bax, Bak and PUMA, as well as down-regulation of that of Bcl-2 and Mcl-1.
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Zhong-Hua
authors: ZH
authors: Li
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Dong-Xiao
authors: DX
authors: Yang
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Peng-Fei
authors: PF
authors: Geng
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Ji
authors: J
authors: Zhang
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Hao-Ming
authors: HM
authors: Wei
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Biao
authors: B
authors: Hu
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Qian
authors: Q
authors: Guo
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Xin-Hui
authors: XH
authors: Zhang
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Wen-Ge
authors: WG
authors: Guo
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China.
authors: Bing
authors: B
authors: Zhao
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: zzuyubin@hotmail.com.
authors: Bin
authors: B
authors: Yu
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: yingdejiqing1314@163.com.
authors: Li-Ying
authors: LY
authors: Ma
authors: School of Pharmaceutical Science & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
authors: Hong-Min
authors: HM
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056466:Histone Demethylases / Q000037:antagonists & inhibitors; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D011743:Pyrimidines; D014230:Triazoles; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Antiproliferative; Apoptosis; Hydrazone; Pyrimidine; Triazole