Design,Synthesis, and Anti-Tumor Activity of 4′-Thionucleosides as Potent and Selective Agonists at the Human A3 Adenosine Receptor |
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Authors: | Lak Shin Jeong Hyuk Woo Lee Hea Ok Kim Ji Young Jung Prashantha Gunaga Sang Kook Lee |
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Institution: | 1. College of Pharmacy , Ewha Womans University , Seoul, Korea;2. College of Pharmacy , Seoul National University , Seoul, Korea |
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Abstract: | On the basis of potent and selective binding affinity of Cl-IB-MECA to the human A3 adenosine receptor, its 4′-thioadenosine derivatives were efficiently synthesized starting from D-gulonic γ -lactone. Among compounds tested, 2-chloro-N 6-(3-iodobenzyl)- and 2-chloro-N 6-methyl-4′ -thioadenosine-5′ -methyluronamides (7a and 7b) exhibited nanomolar range of binding affinity (K i = 0.38 nM and 0.28 nM, respectively) at the human A3AR. These compounds showed anti-growth effects on HL-60 leukemia cell, which resulted from the inhibition of Wnt signaling pathway. |
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Keywords: | Bioisosteric 4′-thionucleosides A3 adenosine receptor agonist anti-proliferative effect |
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