engleski

Conjugates of ferrocene and purine and purine isosteres: synthesis and biological evaluation

On account of their extensive biological activity, nucleoside analogs present an important role as chemotherapeutic agents.[1, 2] In recent years it has been observed that incorporation of organometallic fragments into biomolecules provides compounds with antitumor activity.[3] Taking into consideration the biological relevance of ferrocene and nucleoside analogs, novel purine and purine isosteres containing a ferrocene N-1-substituted 1, 2, 3-triazole (11a- c, 12a-c, 13a-c, 14a-c, 15a-c, 16a, 23a-c, 24a-c, 25a-c) and a ferrocene 4-substituted 1, 2, 3- triazole moiety (34a-c, 35a-c) attached to variety of heterocyclic bases were prepared using copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction of corresponding azidoferrocene precursors and propargylated purine derivatives. Of all tested compounds, ferrocene conjugates 11c (IC50 = 9.07 μM), 13a (IC50 = 14.38 μM) and 15b (IC50 = 15.50 μM) displayed marked antiproliferative activity against colorectal adenocarcinoma cell line. ADME properties (kinetic solubility, microsomal stability and permeability) of synthesized compounds were also studied. Preliminary results of 13a and 15a showed their high solubility and moderate metabolic stability.

purine ; ferrocene ; cytostatic activity ; permeability ; microsomal stability

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