title: One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties.
abstract: A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound 28 showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50 values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 28 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.
authors.affiliation: Department of Microbiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Ma
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Hai-Kui
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Meng-Jin
authors.initials: MJ
authors.lastname: Hu
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Tian-Zhu
authors.initials: TZ
authors.lastname: Ma
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Rui-Yuan
authors.initials: RY
authors.lastname: Liu
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: You
authors.affiliation: Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D010880:Piperidines; D011743:Pyrimidines; C017205:2,4-diaminopyrimidine; D000077489:Piperazine; C032727:piperidine
keywords: 2,4-Diaminopyrimidines; Antiproliferative activity; One-pot synthesis; Piperazine; Piperidine