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
  • 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: [email protected].
  • 4. Department of Chemistry, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
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.