Synthesis and antiproliferative activity of conjugates of adenosine with muramyl dipeptide and nor-muramyl dipeptide derivatives

  • Bioorg Med Chem Lett. 2014 Aug 1;24(15):3587-91. doi: 10.1016/j.bmcl.2014.05.043.
Monika Samsel  1 ,  Krystyna Dzierzbicka  2 ,  Piotr Trzonkowski  3
Affiliations
  • 1. Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.
  • 2. Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland. Electronic address: [email protected].
  • 3. Department of Clinical Immunology and Transplantology, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland.
PMID: 24915876 DOI: 10.1016/j.bmcl.2014.05.043
Abstract

We synthesized a series of MDP(D,D) and nor-MDP(D,D) derivatives conjugated with adenosine through a spacer as potential immunosuppressants. New conjugates 8a-k were evaluated on two leukemia cell lines (Jurkat and L1210) and PBMC from healthy donors. The conjugates 8a-k and MDP(D,D)/nor-MDP(D,D) derivatives 7e, f, i, j were active against L1210 cell line. Unconjugated nor-MDP(D,D) had better antiproliferative properties, but the conjugates 8b, f, g had the highest values of selectivity index. Both cell lines as well as PBMC were resistant to analogs 11a, b with the 6-aminohexanoic linker.

Keywords
Adenosine; Biological activity; MDP(D,D); Muramyl dipeptide conjugates; Nor-MDP(D,D); Synthesis.