title: Design, synthesis and antiproliferative activity evaluation of m-(4-morpholinyl-1,3,5-triazin-2-yl)benzamides in vitro.
abstract: In the present study, a series of m-(4-morpholino-1,3,5-triazin-2-yl)benzamides were designed, synthesized and characterized. Their antiproliferative activities against HCT-116 cell and MCF-7 cell at 10μM were evaluated by MTT assay. Compounds T6, T10, T11, T12 and T19 exhibited potent antiproliferative activities. Thus, their IC50 values against HCT-116 cell, MCF-7 cell, Hela cell, U-87 MG cell and A549 cell were measured. The SAR of the target compounds was preliminary discussed. The Western bolt assay suggested that compound T11 can block the PI3K/Akt/mTOR pathway. Hoechst staining assay indicated that compound T11 can cause morphological changes and induce apoptosis of HCT-116 cells. These findings directly identify the m-(4-morpholinyl-1,3,5-triazin-2-yl)benzamide derivatives as novel antiproliferative agents and further verify the value of the benzamide fragment in drug design.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Genetics and Molecular Biology, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Min-Hang
authors.initials: MH
authors.lastname: Xin
authors.affiliation: Department of Genetics and Molecular Biology, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: She-Min
authors.initials: SM
authors.lastname: Lu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: sqzhang@xjtu.edu.cn.
authors.forename: San-Qi
authors.initials: SQ
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C037689:benzamide
keywords: 1,3,5-Triazine; Antiproliferative activity; Benzamide; Synthesis