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

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

Affiliations

  • 1 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
  • 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: youww@smu.edu.cn.
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.

Figures