title: Synthesis and antiproliferative activity of conjugates of adenosine with muramyl dipeptide and nor-muramyl dipeptide derivatives.
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.
authors.affiliation: Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Samsel
authors.affiliation: Department of Organic Chemistry, Gdansk University of Technology, ul. Narutowicza 11/12, 80-233 Gdansk, Poland. Electronic address: krydzier@pg.gda.pl.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Dzierzbicka
authors.affiliation: Department of Clinical Immunology and Transplantology, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000241:Adenosine / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000241:Adenosine
keywords: Adenosine; Biological activity; MDP(D,D); Muramyl dipeptide conjugates; Nor-MDP(D,D); Synthesis