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. Epub 2016 Apr 16.

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.

MeSH terms

  • Acetates / chemistry*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Acetates
  • Antineoplastic Agents
  • Pyrimidines