Design, synthesis and antiproliferative activity of novel 5-nitropyrimidine-2,4-diamine derivatives bearing alkyl acetate moiety

  • Eur J Med Chem. 2016 Aug 8:118:161-9. doi: 10.1016/j.ejmech.2016.04.038.
Pei-Liang Zhao  1 ,  Yan-Hong Li  2 ,  Hai-Kui Yang  2 ,  Peng Chen  2 ,  Bei Zhang  2 ,  Qi Sun  2 ,  Qiu Li  2 ,  Wen-Wei You  3
Affiliations
  • 1. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
  • 2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
  • 3. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: [email protected].
PMID: 27128180 DOI: 10.1016/j.ejmech.2016.04.038
Abstract

In order to discover new Anticancer drug leads, a series of novel alkylamino pyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Biological evaluation with four human Cancer cell lines (MDA-MB-231, A549, HepG2, and MCF-7) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 7w displayed a three-fold improvement compared with commercial Anticancer drug fluorouracil in inhibiting HepG2 cell proliferation with IC50 value of 10.37 μM. Moreover, flow-activated cell sorting analysis suggested that compound 7w mainly arrested HepG2 cells in G2/M stage. Hence, it could serve as a promising lead for the design of novel Anticancer small-molecule drugs.

Keywords
2,4-Diaminopyrimidines; Alkylamino pyrimidines; Antiproliferative activity; Synthesis.