2. Academic Validation
  3. Polar 3-alkylidene-5-pivaloyloxymethyl-5'-hydroxymethyl-gamma-lactones as protein kinase C ligands and antitumor agents

Polar 3-alkylidene-5-pivaloyloxymethyl-5'-hydroxymethyl-gamma-lactones as protein kinase C ligands and antitumor agents

  • Bioorg Med Chem Lett. 2010 Feb 1;20(3):1008-12. doi: 10.1016/j.bmcl.2009.12.058.
Ji-Hye Kang 1,  Yerim Kim,  Shin-Hye Won,  Song-Kyu Park,  Chang Woo Lee,  Hwan-Mook Kim,  Nancy E Lewin,  Nicholas A Perry,  Larry V Pearce,  Daniel J Lundberg,  Robert J Surawski,  Peter M Blumberg,  Jeewoo Lee
Affiliations

Affiliation

  • 1 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.
PMID: 20045644 DOI: 10.1016/j.bmcl.2009.12.058
Abstract

A series of DAG-lactones with polar 3-alkylidene substituents have been investigated as PKC-alpha ligands and antitumor agents. Extensive analysis of structure-activity relationships for the 3-alkylidene chain revealed that polar groups such as ether, hydroxyl, aldehyde, ester, acyloxy, and amido were tolerated with similar binding affinities and reduced lipophilicities compared to the corresponding unsubstituted alkylidene chain. Among the derivatives, compounds 5, 6 and 8 with an ether type of side chain showed high binding affinities in range of K(i)= 3-5 nM and excellent antitumor profiles, particularly against the colo205 colon Cancer and the K562 leukemia cell lines.

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