2. Academic Validation
  3. Synthesis and evaluation of the NSCLC anti-cancer activity and physical properties of 4-aryl-N-phenylpyrimidin-2-amines

Synthesis and evaluation of the NSCLC anti-cancer activity and physical properties of 4-aryl-N-phenylpyrimidin-2-amines

  • Bioorg Med Chem Lett. 2017 Oct 15;27(20):4749-4754. doi: 10.1016/j.bmcl.2017.08.063.
Borvornwat Toviwek 1,  Praphasri Suphakun 2,  Kiattawee Choowongkomon 2,  Supa Hannongbua 1,  M Paul Gleeson 3
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
  • 2 Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
  • 3 Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand; Department of Biomedical Engineering, Faculty of Engineering, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand. Electronic address: paul.gl@kmitl.ac.th.
PMID: 28927795 DOI: 10.1016/j.bmcl.2017.08.063
Abstract

Reported herein are efforts to profile 4-aryl-N-phenylpyrimidin-2-amines in terms of their anti-cancer activity towards non small-cell lung carcinoma (NSCLC) cells. We have synthesized new 4-aryl-N-phenylpyrimidin-2-amines and assessed them in terms of their cytotoxicity (A549, NCI-H187, MCF7, Vero & KB) and physicochemical properties (logD7.4 and solubility). 13f and 13c demonstrated potent anti-cancer activity in A549 cells (0.2µM), compared to 0.4μM for the NSCLC drug Doxorubicin. 13f also displayed low experimental logD7.4 (2.9) and the best solubility (∼40μM). Compounds 13b and 13d showed the best balance of A549 anti-cancer activity and selectivity. 13g showed good activity and selectivity comparable with the anti-cancer drug Doxorubicin.

Keywords

A549; Computational design; Cytotoxicity; Lipophilicity; Solubility.

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