2. Academic Validation
  3. One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties

One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties

  • Eur J Med Chem. 2014 Sep 12:84:127-34. doi: 10.1016/j.ejmech.2014.07.017.
Wei-Feng Ma 1,  Hai-Kui Yang 2,  Meng-Jin Hu 2,  Qian Li 2,  Tian-Zhu Ma 2,  Zhong-Zhen Zhou 2,  Rui-Yuan Liu 2,  Wen-Wei You 3,  Pei-Liang Zhao 4
Affiliations

Affiliations

  • 1 Department of Microbiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, PR China.
  • 2 Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
  • 3 Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
  • 4 Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
PMID: 25016234 DOI: 10.1016/j.ejmech.2014.07.017
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.

Keywords

2,4-Diaminopyrimidines; Antiproliferative activity; One-pot synthesis; Piperazine; Piperidine.

Figures